Genetics Genetics Vocab: Gene a heritable factor that controls a specific characteristic. Allele one specific form of a gene, differing from other alleles by one or a few bases only and occupying the same locus as other alleles of the gene. Genome The whole of the genetic information of an organism gene mutation a change in the base sequence of a gene. Base substitution The smallest possible change is when one base in a gene is replaced by another. An example of this type of mutation is sickle cell anemia Meiosis a reduction division of a diploid nucleus to form haploid nuclei. Homologous chromosomes chromosomes with the same genes in the same loci but not necessarily the same alleles of those genes. Random orientation during prophase I the position of each pair of chromosomes when the spindle attaches is random Non-‐disjunction sometimes chromosomes that should separate and move to opposite poles during meiosis do not separate and instead they both move to the same pole Karyotyping chromosomes are arranged in pairs according to their size. Performed using cells collected by chorionic villus sampling for prenatal diagnosis of chromosome abnormalities. Prophase I Chromosome supercoil, homologous chromosomes ( bivalents) pair up (synapsis), crossing over occurs resulting in chiasma, centrioles move to opposite poles in animal cells and the nuclear membrane breaks down. Metaphase I spindle microtubules attach to centromeres, bivalents line up at the equator. Anaphase I the two chromosomes of each bivalent move to opposite poles, thus halving the chromosome number, each chromosome consists of two identical sister chromatids, if crossing over occurred they are not identical.
Telophase I nuclear membranes form, the cell divides to form two haploid cells Prophase II Chromosome supercoil, homologous chromosomes ( bivalents) pair up (synapsis), crossing over occurs resulting in chiasma, centrioles move to opposite poles in animal cells and the nuclear membrane breaks down. [EXCEPT THERE ARE NO HOMOLOGOUS CHROMOSOMES TO PAIR UP, THUS NO CROSSING OVER] Metaphase II spindle microtubules attach to centromeres, bivalents line up at the equator, at the end of the phase the centromeres divide. Anaphase II The centromeres split, then the two chromatids of each chromosome move to opposite poles Telophase II nuclear membranes form, the cell divides to form two haploid cells [EXCEPT TWO CELLS DIVIDE TO FORM FOUR HAPLOID CELLS WHICH WILL DEVELOP INTO GAMETES, THE CHROMATIDS ARE NOW KNOWN AS CHROMOSOMES synapsis during crossing over in prophase I, all the chromatids of two homologous chromosomes become tightly paired. chiasma where there was crossing over there is an x-‐shaped structure recombination the reassortment of genes or characters into different combinations from those of the parents Independent assortment the way one pair of homologous chromosome is segregated ( assorted) during formation of gametes ( meiosis) is independent of the way any other pair is segregated. ( due to random orientation) autosome a chromosome that has no genes involved with sex determination. Humans have 22 pairs. Sex chromosome a chromosome that has genes involved with sex determination. Humans have 1 pair. Linkage group all of the genes that have their loci on the same chromosome. Polygenic inheritance inheritance of characteristics controlled by more than one gene.
Genotype the alleles of an organism Phenotype the characteristics of an organism. Dominant allele an allele that has the same effect on the phenotype whether it is present in the homozygous or heterozygous state Recessive allele an allele that only has an effect on the phenotype when present in the homozygous state Codominant allele pairs of alleles that both affect the phenotype when present in a heterozygote Locus the particular position on homologous chromosomes of a gene homozygous having two identical alleles of a gene heterozygous having two different alleles of a gene. carrier an individual that has one copy of a recessive allele that causes a genetic disease in individuals that are homozygous for this allele test cross testing a suspected heterozygote by crossing it with a known homozygous recessive multiple alleles some genes have more than two alleles ABO blood group are an example of codominance and multiple alleles blood type O ii blood type A I^AI^A or I^Ai blood type B I^BI^B or I^Bi blood type AB I^AI^B
sex linkage the association of a characteristic with gender, because the gene controlling the characteristic is located on a sex chromosome. ( usually the X) Hemophilia are produced by a recessive sex allele on the X chromosome. The allele is X^h and the dominant allele is X^H colorblindness are produced by a recessive sex allele on the X chromosome. The allele is X^b and the dominant allele is X^B PCR (polymerase chain reaction) is used to copy and amplify minute quantities of DNA/ Gel e lectrophoresis fragments of DNA move in an electric field and are separated according to their size. Clone a group of genetically identical organisms or a group of cells derived from a single parent.
Genetics Practice problems: Question 1 of 10 Which enzymes are needed to produce recombinant plasmids that are used in gene transfer? A. Restriction enzymes and ligase B. Helicase and restriction enzymes C. DNA polymerase and ligase D. DNA polymerase and restriction enzymes
Question 2 of 10 What constitutes a linkage group? A. Genes controlling a polygenic characteristic B. Alleles for the inheritance of ABO blood groups C. Genes whose loci are on different autosomes D. Genes carried on the same chromosome
Question 3 of 10
A cell with a diploid number of 12 chromosomes undergoes meiosis. What will be the product at the end of meiosis? A. 4 cells each with 12 chromosomes B. 2 cells each with 6 chromosomes C. 4 cells each with 6 chromosomes D. 2 cells each with 12 chromosomes
Question 4 of 10 A parent organism of unknown genotype is mated in a test cross. Half of the offspring have the same phenotype as the parent. What can be concluded from this result? A. The parent is heterozygous for the trait. B. The parent is homozygous recessive for the trait. C. The parent is homozygous dominant for the trait. D. The trait being inherited is polygenic.
Question 5 of 10 Which process results in the greatest genetic variation in a population? A. natural selection B. mitosis C. meiosis D. cytokinesis
Question 6 of 10 A cross is performed between two organisms with the genotypes AaBb and aabb. What genotypes in the offspring are the result of recombination? A. Aabb, AaBb B. aabb, Aabb C. AaBb, aabb D. Aabb, aaBb
Question 7 of 10 What is a difference between autosomes and sex chromosomes? A. Autosomes are not found in gametes but sex chromosomes are. B. Sex chromosomes determine gender and autosomes do not. C. Autosomes are diploid and sex chromosomes are haploid.
D. Sex chromosomes are found in animal cells and autosomes are found in plant cells.
Question 8 of 10 If red (RR) is crossed with white (rr) and produces a pink flower (Rr), and tall (D) is dominant to dwarf (d), what is the phenotypic ratio from a cross of Rr dd and rr Dd? A. 1:1:1:1, in which 50% are tall, 50% dwarf, 50% pink and 50% white B. 3:1 C. 50% pink, 50% white and all tall D. 9:3:3:1
Question 9 of 10 What is a possible consequence of two base substitution mutations occurring in the same gene? A. Amino acids in two polypeptides coded for the gene are changed. B. All of the codons from the first mutation onward are changed. C. Two amino acids coded for the gene are changed. D. All of the codons between the two mutations are changed.
Question 10 of 10 If a person inherited an allele with the same base substitution mutation from both parents, what sequences could be altered from normal in the person's cells? A. One mRNA base sequence only B. One mRNA base sequence and one polypeptide amino acid sequence only C. Two mRNA base sequences only D. Two mRNA base sequences and two polypeptide amino acid sequences only
Answers: ADCAC DBACB Other multiple Choice questions link: http://wps.aw.com/bc_goodenough_boh_3/104/26717/6839635.cw/index.ht ml 1. Explain the difference between incomplete dominance and codominance:
2. In some chickens, the gene for feather color is controlled by codiminance. The allele for black is B and the allele for white is W. The heterozygous phenotype is known as erminette. a. What is the genotype for black chickens? ____ b. What is the genotype for white chickens? ____ c. What is the genotype for erminette chickens? ____ 3. If two erminette chickens were crossed, what is the probability that: a. They would have a black chick? ____% b. They would have a white chick? ____% Parents: ____ X ____ 4. A black chicken and a white chicken are crossed. What is the probability that they will have erminette chicks? ____% Parents: ____ X ____ 5. In snapdragons, flower color is controlled by incomplete dominance. The two alleles are red ( R) and white ( W). The heterozygous genotype is expressed as pink. a. What is the phenotype of a plant with the genotype RR? ___________ b. What is the phenotype of a plant with the genotype WW? ___________ c. What is the phenotype of a plant with the genotype RW? ___________ II. Blood type questions: 1. A man with AB blood is married to a woman with AB blood. What blood types will their children be and in what proportion? 2. A man who has type B blood ( genotype: BB) is married to a woman with type O blood. What blood type will their children have? 3. A woman with type A blood ( genotype: AO) is married to a type B person ( genotype: BO). What blood types will their children have? 4. A woman with type A blood is claiming that a man with type AB blood is the father of her child, who is also type AB. Could this man be the father? Show the possible crosses; remember the woman can have AO or AA genotypes. 5. A man with type AB blood is married to a woman with type O blood. They have two natural children, and one adopted child. The children's blood types are: A, B, and O. Which child was adopted? 6. A person with type A blood ( unknown genotype) marries a person with type O blood. What blood types are possible among their children 7. Two people, both with AB blood have four children. What blood types should the children be? 8. A person with type B blood ( genotype BO) has children with a type AB person. What blood types are possible among their children? 9. A person with type O blood is married to a person with type A blood ( unknown genotype). They have 6 children, 3 of them have type A blood, three of them have type O blood. What is the genotype of the two parents?
10. A person has type B blood. What are ALL the possible blood types of his parents. Show the crosses to prove your answer. 11. A man of unknown genotype has type B blood, his wife has type A blood ( also unknown genotype). List ALL the blood types possible for their children. ( you may need to do multiple crosses to consider the different possible genotypes of the parents) III. Sex-‐linked traits, punnet squares and pedigree Usually, sex-‐linked disorders are recessive disorders found on the X chromosome. Because women have two X chromosomes, they need to inherit two bad X chromosomes to become afflicted with the disease. This is not likely to happen so women with sex-‐linked disorders are very rare. Men however only have one single X chromosome. Therefore if a male has the damaged gene on his only X chromosome he will have the disorder because he does not have a “backup” X chromosome. A male’s Y chromosome does not offset any damage done to the X chromosome. Examples of SexLinked disorders are hemophilia, colorblindness, and muscular dystrophy. 1. Two normal-‐visioned parents produce a colorblind son. Draw a pedigree that includes every person ( 3 people) mentioned in the story. Include a Punnett square of the parents. Draw a Punnett square for the mother and father Draw a pedigree below that shows all three people of this family a. What are the genotypes of the parents? Mom = ________________ Dad = _________________ b. What are the chances of their next child being a colorblind daughter? _______________ c. Before having this first child, what was the probability this couple would have three children, all healthy? 2. In humans, the gene for normal blood clotting ( XH) is dominant to the gene for hemophilia ( Xh). This is a sexlinked trait found on the X chromosome. A woman with normal blood clotting has four children. They are a normal son, a hemophiliac son, and two normal daughters. The father has normal blood clotting. Draw a pedigree that includes every person mentioned in the story. Draw a Punnett square for the mother and father. Draw pedigree below that shows all six people of this family a. Write in the probable genotype next to or inside of each circle and square in your pedigree above. b. If they decide to have another child, what are the chances the child will be a girl who carries the disorder? 3. A man, whose mother is homozygous dominant and whose father is a hemophiliac, marries a woman with no history of hemophilia in her family. The man and woman decide to raise a family and have 3 children, a boy, a girl, and another boy. Draw a pedigree that includes every person mentioned in the story. Include a Punnett square of the man and woman. a. Draw the Punnett Square below showing the man and woman b. Draw pedigree below that shows all seven people in this family c. Write in the probable genotype next to or inside of each circle and square in your pedigree above. d. What are the chances that the man and woman can have a child with hemophilia?
IV. Probability of inheritance 1. A man has six fingers on each hand and six toes on each foot. His wife and their daughter have the normal number of digits ( 5). Extra digits is a dominant trait. What fraction of this couple's children would be expected to have extra digits? 2. Imagine you are a genetic counselor, and a couple planning to start a family came to you for information. Charles was married once before, and he and his first wife had a child who has cystic fibrosis. The brother of his current wife Elaine died of cystic fibrosis. What is the probability that Charles and Elaine will have a baby with cystic fibrosis? ( Neither Charles nor Elaine has the disease) 3. In mice, black color ( B ) is dominant to white ( b ) . At a different locus, a dominant allele ( A ) produces a band of yellow just below the tip of each hair in mice with black fur. This gives a frosted appearance known as agouti. Expression of the recessive allele ( a ) results in a solid coat color. If mice that are heterozygous at both loci are crossed, what will be the expected phenotypic ratio of their offspring?
IB Objectives 4.1 Chromosomes, genes, alleles and mutation 4.1.1 State that eukaryotic chromosomes are made of DNA and protein ❖
Eukaryotic chromosomes consist of DNA wrapped around histone proteins
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This forms the basic structure of the nucleosome, which is packed together to form chromatin (in a 'beads on a string' arrangement)
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Chromatin will supercoil and condense during prophase to form chromosomes that can be visualised under a light microscope
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Prokaryotic DNA is not wrapped around proteins and is thus considered to be 'naked'
Fig: Arrangement of DNA into chromosomes
4.1.2 Define gene, allele and genome
❖ Gene: A heritable factor that controls a specific characteristic, consisting of a length of DNA occupying a particular position on a chromosome (locus) ❖ Allele: One specific form of a gene, differing from other alleles by one or a few bases only and occupying the same locus as other alleles of the gene ❖ Genome: The whole of the genetic information of an organism 4.1.3 Define gene mutation ❖ Gene mutation: A change in the nucleotide sequence of a section of DNA coding for a particular feature 4.1.4 Explain the consequence of a base substitution mutation in relation to the process of transcription and translation using the example of sickle cell anaemia ❖ Cause of Sickle Cell Anaemia ● A base substitution mutation is the change of a single base in a sequence of DNA, resulting in a change to a single mRNA codon during transcription ● In the case of sickle cell anaemia, the 6th codon for the beta chain of haemoglobin is changed from GAG to GTG (on the non-‐coding strand) ● This causes a change in the mRNA codon (GAG to GUG), resulting in a single amino acid change of glutamic acid to valine (Glu to Val) ● • DNA: GAG to GTG (non-‐coding strand) • mRNA: GAG to GUG • Amino Acid: Glu to Val ● The amino acid change alters the structure of haemoglobin, causing it to form fibrous, insoluble strands ● This causes the red blood cell to adopt a sickle shape
Normal Red Blood Cell Sickle Cell
❖ Consequences of Sickle Cell Anaemia ● The insoluble haemoglobin cannot effectively carry oxygen, causing individual to feel constantly tired ● The sickle cells may accumulate in the capillaries and form clots, blocking blood supply to vital organs and causing a myriad of health problems ● Also causes anaemia (low RBC count), as the sickle cells are destroyed more rapidly than normal red blood cells ● Sickle cell anaemia occurs in individuals who have two copies of the codominant 'sickle cell' allele (i.e. homozygotes) ● Heterozygous individuals have increased resistance to malaria due to the presence of a single 'sickle cell' allele (heterozygous advantage)
Fig: Sickle Cell Anaemia
4.2: Meiosis 4.2.1 State that meiosis is a reduction division of a diploid nucleus to form haploid nuclei Meiosis is the process by which sex cells (gametes) are made in the reproductive organs: ❖
Most sexually reproducing animals are diploid -‐ meaning they have two copies of every chromosome (one of maternal origin, one of paternal origin)
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In order to reproduce, these organisms need to make gametes that are haploid (have only one copy of each chromosome)
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Fertilisation of two haploid gametes (egg + sperm) will result in the formation of a diploid zygote that will grow into a new organism
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Meiosis consists of two cell divisions:
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The first division is a reduction division of the diploid nucleus to form haploid nuclei
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The second division separates sister chromatids (this division is necessary because meiosis is preceded by interphase, wherein DNA is replicated)
4.2.2 Define homologous chromosomes Homologous chromosomes are chromosomes that share: ❖
The same structural features (e.g. same size, same banding pattern, same centromere position)
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The same genes at the same loci positions (while genes are the same, alleles may be different)
4.2.3 Outline the process of meiosis, including pairing of homologous chromosomes and crossing over, followed by two divisions, which results in four haploid cells ❖ The process of meiosis involves two divisions, both of which follow the same basic stages as mitosis (prophase, metaphase, anaphase and telophase) ❖ Meiosis is preceded by interphase, which includes the replication of DNA (S phase) to create chromosomes with genetically identical sister chromatids
Meiosis I Homologous chromosomes must first pair up in order to be sorted into separate haploid daughter cells In prophase I, homologous chromosomes undergo a process called synapsis, whereby homologous chromosomes pair up to form a bivalent (or tetrad) ■
The homologous chromosomes are held together at points called chiasma (singular: chiasmata)
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Crossing over of genetic material between non-‐sister chromatids can occur at these points, resulting in new gene combinations (recombination)
The remainder of meiosis I involves separating the homologous chromosomes into separate daughter cells ■
In metaphase I, the homologous pairs line up along the equator of the cell
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In anaphase I, the homologous chromosomes split apart and move to opposite poles
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In telophase I, the cell splits into two haploid daughter cells as cytokinesis happens concurrently
Meiosis II In meiosis II, the sister chromatids are divided into separate cells
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In prophase II, spindle fibres reform and reconnect to the chromosomes
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In metaphase II, the chromosomes line up along the equator of the cell
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In anaphase II, the sister chromatids split apart and move to opposite poles
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In telophase II, the cell splits in two as cytokinesis happens concurrently
Because sister chromatids may no longer be genetically identical as a result of potential recombination, the process of meiosis results in the formation of four genetically distinct haploid daughter cells 4.2.4 Explain that non-‐disjunction can lead to a change in chromosome number, illustrated by reference to Down syndrome (trisomy 21) Non-‐disjunction refers to the chromosomes failing to separate correctly, resulting in gametes with one extra, or one missing, chromosome (aneuploidy) The failure of the chromosomes to separate may either occur via: ■
Failure of homologues to separate during Anaphase I (resulting in four affected daughter cells)
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Failure of sister chromatids to separate during Anaphase II (resulting in two affected daughter cells)
Non-‐Disjunction
Individuals with Down syndrome have three copies of chromosome 21 (trisomy 21) ■
One of the parental gametes had two copies of chromosome 21 as a result of non-‐disjunction
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The other parental gamete was normal and had a single copy of chromosome 21
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When the two gametes fused during fertilisation, the resulting zygote had three copies of chromosome 21, leading to Down syndrome
4.2.5 State that, in karyotyping, chromosomes are arranged in pairs according to their structure A karyotype is a visual profile of all the chromosomes in a cell The chromosomes are arranged into homologous pairs and displayed according to their structural characteristics Human Male Karyotype
Karyotyping involves: ■
Harvesting cells (usually from foetus or white blood cells of adults)
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Chemically inducing cell division, then halting it during mitosis when chromosomes are condensed and thus visible The stage during which mitosis is halted will determine whether chromosomes appear with sister chromatids Staining and photographing chromosomes, before arranging them according to ■
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structure 4.2.6 State that karyotyping is performed using cells collected by chorionic villus sampling or amniocentesis, for pre-‐natal diagnosis of chromosome abnormalities Pre-‐natal karyotyping is often used to: ■
Determine the gender of an unborn child (via identification of sex chromosomes)
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Test for chromosomal abnormalities (e.g. aneuploidies resulting from non-‐disjunction)
Amniocentesis ■
A needle is inserted through the abdominal wall, into the amniotic cavity in the uterus, and a sample of amniotic fluid containing foetal cells is taken
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It can be done at ~ 16th week of pregnancy, with a slight chance of miscarriage (~0.5%)
Chorionic Villus Sampling ■
A tube is inserted through the cervix and a tiny sample of the chorionic villi (contains foetal cells) from the placenta is taken
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It can be done at ~ 11th week of pregnancy, with a slight risk of inducing miscarriage (~1%)
Amniocentesis Chorionic Villus Sampling
4.2.7 Analyse a human karyotype to determine gender and whether non-‐disjunction has occurred Every cell in the human body has 46 chromosomes (except anucleate red blood cells and haploid gametes) Males (X,Y) and females (X,X) can be differentiated on the basis of their sex chromosomes Non-‐disjunction during gamete formation can lead to individuals with an abnormal number of chromosomes (aneuploidy) These disorders can be classified according to the chromosome number affected and the number of chromosomes present Analysing Karyotypes 4.3.1 Define genotype, phenotype, dominant allele, recessive allele, codominant alleles, locus, homozygous, heterozygous, carrier and test cross
Genotype: The allele combination of an organism Phenotype: The characteristics of an organism (determined by a combination of genotype and environmental factors) Dominant Allele: An allele that has the same effect on the phenotype whether it is present in the homozygous or heterozygous state Recessive Allele: An allele that only has an effect on the phenotype when present in the homozygous state Codominant Alleles: Pairs of alleles that both affect the phenotype when present in a heterozygote Locus: The particular position on homologous chromosomes of a gene Homozygous: Having two identical alleles of a gene Heterozygous: Having two different alleles of a gene Carrier: An individual that has one copy of a recessive allele that causes a genetic disease in individuals that are homozygous for this allele Test Cross: Testing a suspected heterozygote by crossing it with a known homozygous recessive 4.3.2 Determine the genotypes and phenotypes of the offspring of a monohybrid cross using a Punnett grid A genetic cross is a means of determining the genetic characteristics of potential offspring based on the genetic characteristics of the prospective parents A monohybrid cross determines the allele combinations of offspring for one particular gene only (HL students may refer to topic 10.2 for dihybrid crosses)
Monohybrid crosses can be calculated according to the following steps: Step 1: Designate characters to represent the alleles
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Capital letter for dominant allele, lower case letter for recessive allele
Step 2: Write down the genotype and phenotype of the parents ■
This is the P generation (parental generation)
Step 3: Write down the genotype of the parental gametes ■
These will be haploid as a result of meiotic division
Step 4: Use a Punnett grid to work out the potential gamete combinations ■
As fertilisation is random, all combinations have an equal probability
Step 5: Write out the genotype and phenotype ratios of potential offspring ■
This is the F1 generation (first filial generation)
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Subsequent generations through interbreeding labeled F2, F3, etc.
Note: The genotypic and phenotypic ratios calculated are only probabilities 4.3.3 State that some genes have more than two alleles (multiple alleles) Some genes have more than two alleles for a given trait (e.g. the ABO blood group system) The alleles which are not recessive may either: ■
Share codominance (be expressed equally in the phenotype)
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Share incomplete dominance (neither is fully expressed in the phenotype, resulting in blending)
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Demonstrate a dominance order (e.g. allele A > allele B > allele C)
4.3.4 Describe ABO blood groups as an example of codominance and multiple alleles When assigning alleles for codominance, the convention is to use a common letter to represent dominant and recessive and use superscripts to represent the different codominant alleles ■
I stands for immunoglobulin (antigenic protein on blood cells)
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A and B stand for the codominant variants
The ABO gene has three alleles: IA, IB and i ■
IA and IB are codominant, wherease i is recessive (no antigenic protein is produced)
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Codominance means that both IA and IB alleles will be expressed within a given phenotype
The genotypes and phenotypes of the ABO blood groups are:
The ABO Blood Group System
4.3.5 Explain how sex chromosomes control gender by referring to the inheritance of X and Y chromosomes in humans Humans have 23 pairs of chromosomes for a total of 46 (excluding instances of aneuploidy) The first 22 pairs are autosomes -‐ each chromosome pair possesses the same genes and structural features The 23rd pair of chromosomes are heterosomes (or sex chromosomes) and determine gender ■
Females are XX -‐ they possess two X chromosomes
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Males are XY -‐ they posses one X chromosome and a much shorter Y chromosome
The Y chromosome contains the genes for developing male sex characteristic -‐ hence the father is always responsible for determining gender
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If the male sperm contains the X chromosome the growing embryo will develop into a girl
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If the male sperm contains a Y chromosome the growing embryo will develop into a boy
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In all cases the female egg will contain an X chromosome (as the mother is XX)
Because the X and Y chromosomes are of a different size, they cannot undergo crossing over / recombination during meiosis This ensures that the gene responsible for gender always remains on the Y chromosome, meaning that there is always ~ 50% chance of a boy or girl 4.3.6 State that some genes are present on the X chromosome and absent from the shorter Y chromosome The Y chromosome is much shorter than the X chromosome and contains only a few genes ■
Includes the SRY sex-‐determination gene and a few
others (e.g. hairy ears gene) The X chromosome is much longer and contains several genes not present on the Y chromosome ■
Includes the genes for haemophilia and red-‐green colour
blindness In human females, only one of the X chromosomes remains active throughout life
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The other is packaged as heterochromatin to form a condensed Barr body
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This inactivation is random and individual to each cell, so heterozygous women will be a mosaic -‐ expressing both alleles via different cells
4.3.7 Define sex linkage Sex linkage refers to when a gene controlling a characteristic is found on a sex chromosome (and so we associate the trait with a predominant gender) ■
Sex-‐linked conditions are usually X-‐linked, as very few genes exist on the shorter Y chromosome
4.3.8 Describe the inheritance of colour blindness and haemophilia as examples of sex linkage ■
Colour blindness and haemophilia are both examples of X-‐linked recessive conditions
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The gene loci for these conditions are found on the non-‐homologous region of the X chromosome (they are not present of the Y chromosome)
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As males only have one allele for this gene they cannot be a carrier for the condition
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This means they have a higher frequency of being recessive and expressing the trait
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Males will always inherit an X-‐linked recessive condition from their mother
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Females will only inherit an X-‐linked recessive condition if they receive a recessive allele from both parents
When assigning alleles for sex-‐linked traits the convention is to write the allele as a superscript to the sex chomosome (usually X) ■
Haemophilia: XH = unaffected ; Xh = affected
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Colour Blindness: XA = unaffected ; Xa = affected
Male and Female Genotypes for a Sex-‐Linked Condition
4.3.9 State that a human female can be homozygous or heterozygous with respect to sex-‐linked genes As human females have two X chromosomes (and therefore two alleles for any given X-‐linked gene), they can be either homozygous or heterozygous Males only have one X chromosome (and therefore only one allele) and are hemizygous 4.3.10 Explain that female carriers are heterozygous for X-‐linked recessive alleles ■
An individual with a recessive allele for a disease condition that is masked by a normal dominant allele is said to be a carrier
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Carriers are heterozygous and can potentially pass the trait on to the next generation, but do not suffer from the defective condition themselves
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Females can be carriers for X-‐linked recessive conditions because they have two X chromosomes -‐ males (XY) cannot be carriers
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Because a male only inherits an X chromosome from his mother, his chances of inheriting the disease condition from a carrier mother is greater
4.3.11 Predict the genotypic and phenotypic ratios of offspring of monohybrid crosses involving any of the above patterns of inheritance Autosomal Dominance / Recessive ■
Choose a letter where the upper and lower case forms are easily distinguishable (e.g. E/e, A/a, B/b)
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Use the capital letter for the dominant allele and the lower case letter for the recessive allele
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Example:
Codominance ■
Choose a letter to denote the general trait encoded by the gene (capital = dominant, lower case = recessive)
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Use different superscript letters (capitals) to represent the different codominant alleles
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Example:
X-‐linked Recessive ■
Use a capital "X" to denote the X chromosome
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Choose a superscript letter to represent the trait (capital = dominant, lower case = recessive)
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Example:
4.3.12 Deduce the genotype and phenotype of individuals in pedigree charts A pedigree is a chart of the genetic history of a family over several generations ■
Males are represented as squares, while females are represented as circles
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Shaded symbols means an individual is affected by a condition, while an unshaded symbol means they are unaffected
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A horizontal line between a man and woman represents mating and resulting children are shown as offshoots to this line
Autosomal Dominance ■
All affected individuals must have at least one affected parent
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If two parents are unaffected, all offspring must be unaffected (homozygous recessive)
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If two parents are affected, they may have offspring who are unaffected (if parents are heterozygous)
Autosomal Recessive ■
If two parents show a trait, all children must also show the trait (homozygous recessive)
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An affected individual may have two normal parents (if parents are both heterozygous carriers)
X-‐Linked Recessive ■
If a female shows the trait, so must all sons as well as her father
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The disorder is more common in males
Identifying Modes of Inheritance
4.4.1 Outline the use of polymerase chain reaction (PCR) to copy and amplify minute quantities of DNA
PCR is a way of producing large quantites of a specific target sequence of DNA It is useful when only a small amount of DNA is avaliable for testing
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E.g. crime scene samples of blood, semen, tissue, hair, etc.
PCR occurs in a thermal cycler and involves a repeat procedure of 3 steps: 1. Denaturation: DNA sample is heated to separate it into two strands 2. Annealing: DNA primers attach to opposite ends of the target sequence 3. Elongation: A heat-‐tolerant DNA polymerase (Taq) copies the strands One cycle of PCR yields two identical copies of the DNA sequence ■
A standard reaction of 30 cycles would yield 1,073,741,826 copies of DNA (230)
4.4.2 State that, in gel electrophoresis, fragments of DNA can move in an electric field and are separated according to their size Gel electrophoresis is a technique which is used to separate fragments of DNA according to size
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Samples of fragmented DNA are placed in the wells of an agarose gel
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The gel is placed in a buffering solution and an electrical current is passed across the gel
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DNA, being negatively charged (due to phosphate), moves to the positive terminus (anode)
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Smaller fragments are less impeded by the gel matrix and move faster through the gel
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The fragments are thus separated according to size
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Size can be calculated (in kilobases) by comparing against a known industry standard
4.4.3 State that gel electrophoresis of DNA is used in DNA profiling ■
DNA profiling is a technique by which individuals are identified on the basis of their respective DNA profiles
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Within the non-‐coding region of an individual's genome, there exists satellite DNA -‐ long stretches of DNA made up of repeating elements called short tandem repeats (STRs)
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These repeating sequences can be excised to form fragments, by cutting with a variety of restriction endonucleases (which cut DNA at specific sites)
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As individuals all have a different number of repeats in a given sequence of satellite DNA, they will all generate unique fragment profiles
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These different profiles can be compared using gel electrophoresis DNA Profiling Using STR Analysis
4.4.4 Describe the application of DNA profiling to determine paternity and also in forensic investigation ■
A DNA sample is collected (blood, saliva, semen, etc.) and amplified using PCR
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Satellite DNA (non-‐coding) is cut with specific restriction enzymes to generate fragments
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Individuals will have unique fragment lengths due to the variable length of their short tandem repeats (STR)
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The fragments are separated with gel electrophoresis (smaller fragments move quicker through the gel)
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The DNA profile can then be analysed according to need
Two applications of DNA profiling are: ■
Paternity testing (comparing DNA of offspring against potential fathers)
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Forensic investigations (identifying suspects or victims based on crime-‐scene DNA)
4.4.5 Analyse DNA profiles to draw conclusions about paternity or forensic investigations Paternity Testing: Children inherit half of their alleles from each parent and thus should possess a combination of their parents alleles Forensic Investigation: Suspect DNA should be a complete match with the sample taken from a crime scene if a conviction is to occur Paternity Test Forensic Investigation
4.4.6 Outline three outcomes of the sequencing of the complete human genome The Human Genome Project (HGP) was an international cooperative venture established to sequence the 3 billion base pair (~25,000 genes) in the human genome The outcomes of this project include: ■
Mapping: We now know the number, location and basic sequence of human genes
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Screening: This has allowed for the production of specific gene probes to detect sufferers and carriers of genetic disease conditions
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Medicine: With the discovery of new proteins and their functions, we can develop improved treatments (pharmacogenetics and rational drug design)
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Ancestry: It will give us improved insight into the origins, evolution and historical migratory patterns of humans
With the completion of the Human Genome Project in 2003, researcher have begun to sequence the genomes of several non-‐human organisms In Situ Hybridisation
4.4.7 State that, when genes are transferred between species, the amino acid sequence of polypeptides translated from them is unchanged because the genetic code is universal The genetic code is universal, meaning that for every living organism the same codons code for the same amino acids (there are a few rare exceptions) This means that the genetic information from one organism could be translated by another (i.e. it is theoretically transferable) Current Examples of Transgenic Modification 4.4.8 Outline a basic technique used for gene transfer involving plasmids, a host cell (bacterium, yeast or other cell), restriction enzymes (endonucleases) and DNA ligase 1. DNA Extraction ■
A plasmid is removed from a bacterial cell (plasmids are small, circular DNA molecules that can exist and replicate autonomously)
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A gene of interest is removed from an organism's genome using a restriction endonuclease which cut at specific sequences of DNA
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The gene of interest and plasmid are both amplified using PCR technology
2. Digestion and Ligation ■
The plasmid is cut with the same restriction enzyme that was used to excise the gene of interest
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Cutting with certain restriction enzymes may generate short sequence overhangs ("sticky ends") that allow the the two DNA constructs to fit together
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The gene of interest and plasmid are spliced together by DNA ligase creating a recombinant plasmid
3. Transfection and Expression ■
The recombinant plasmid is inserted into the desired host cells (this is called transfection for eukaryotic cells and transformation for prokaryotic cells)
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The transgenic cells will hopefully produce the desired trait encoded by the gene of interest (expression)
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The product may need to subsequently be isolated from the host and purified in order to generate sufficient yield
Treating Haemophilia via the Isolation of Human Factor IX Clotting Protein from Transgenic Sheep Milk
4.4.9 State two examples of current uses of genetically modified crops or animals Crops 1. Engineering crops to extend shelf life of fresh produce ■
Tomatoes (Flavr Savr) have been engineered to have an extended keeping quality by switching off the gene for ripening and thus delaying the natural process of softening of fruit
2. Engineering of crops to provide protection from insects
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Maize crops (Bt corn) have been engineered to be toxic to the corn borer by introducing a toxin gene from a bacterium (Bacillus thuringiensis)
Animals 1. Engineering animals to enhance production ■
Sheep produce more wool when engineered with the gene for the enzyme responsible for the production of cysteine -‐ the main amino acid in the keratin protein of wool
2. Engineering animals to produce desired products ■
Sheep engineered to produce human alpha-‐1-‐antitrypsin in their milk can be used to help treat individuals suffering from hereditary emphysema
4.4.10 Discuss the potential benefits and potential harmful effects of one example of genetic modification Example: Maize introduced with a bacterial gene encoding a toxin to the European Corn Borer (i.e. Bt Corn) Potential Benefits ■
Allows for the introduction of a characteristic that wasn't present within the gene pool (selective breeding could not have produced desired phenotype)
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Results in increased productivity of food production (requires less land for comparable yield)
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Less use of chemical pesticides, reducing the economic cost of farming
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Can now grow in regions that, previously, may not have been viable (reduces need for deforestation)
Potential Harmful Effects ■
Could have currently unknown harmful effects (e.g. toxin may cause allergic reactions in a percentage of the population)
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Accidental release of transgenic organism into the environment may result in competition with native plant species
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Possibility of cross pollination (if gene crosses the species barrier and is introduced to weeds, may have a hard time controlling weed growth)
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Reduces genetic variation / biodiversity (corn borer may play a crucial role in local ecosystem)
4.4.11 Define clone A clone is a group of genetically identical organisms or a group of cells derived from a single parent cell 4.4.12 Outline a technique for cloning using differentiated animal cells Somatic Cell Nuclear Transfer (SCNT) is a method of reproductive cloning using differentiated animal cells ■
A female animal (e.g. sheep) is treated with hormones (such as FSH) to stimulate the development of eggs
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The nucleus from an egg cell is removed (enucleated), thereby removing the genetic information from the cell
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The egg cell is fused with the nucleus from a somatic (body) cell of another sheep, making the egg cell diploid
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An electric shock is delivered to stimulate the egg to divide, and once this process has begun the egg is implanted into the uterus of a surrogate
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The developing embryo will have the same genetic material as the sheep that contributed the diploid nucleus, and thus be a clone
Different Uses of Cloning
4.4.13 Discuss the ethical issues of therapeutic cloning in humans ■
Refer to Topic 2.1.10 for an outline of uses for therapeutic cloning in humans
Arguments for Therapeutic Cloning ■
May be used to cure serious diseases or disabilities with cell therapy (replacing bad cells with good ones)
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Stem cell research may pave the way for future discoveries and beneficial technologies that would not have occurred if their use had been banned
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Stem cells can be taken from embryos that have stopped developing and would have died anyway (e.g. abortions)
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Cells are taken at a stage when the embryo has no nervous system and can arguably feel no pain
Arguments Against Therapeutic Cloning
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Involves the creation and destruction of human embryos (at what point do we afford the right to life?)
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Embryonic stem cells are capable of continued division and may develop into cancerous cells and cause tumors
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More embryos are generally produced than are needed, so excess embryos are killed
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With additional cost and effort, alternative technologies may fulfil similar roles (e.g. nuclear reprogramming of differentiated cell lines)
10.1.1 Describe the behaviour of the chromosomes in the phases of meiosis Interphase: Cell growth and DNA replication (duplication of DNA creates sister chromatid chromosomes) Meiosis I ■
Prophase I: DNA supercoils and chromosomes condense, nuclear membrane dissolves, homologous pairs form bivalents, crossing over occurs
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Metaphase I: Spindle fibres from centrioles (at poles) attach to centromeres of bivalent, bivalents line up along the equator of the cell
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Anaphase I: Spindle fibres contract and split the bivalent, homologous chromosomes move to opposite poles of the cell
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Telophase I: Chromosomes decondense, nuclear membranes may reform, cell divides (cytokinesis) forming two haploid daughter cells
Interkinesis: An optional rest period between meiosis I and meiosis II, no DNA replication occurs in this stage
Meiosis II ■
Prophase II: Chromosomes condense, nuclear membrane dissolves (if reformed), centrioles move to opposite poles (perpendicular to previous poles)
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Metaphase II: Spindle fibres from centrioles attach to centromeres of chromosomes, chromosomes line up along the equator of the cell
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Anaphase II: Spindle fibres contract and split the chromosome into sister chromatids, chromatids (now called chromosomes) move to opposite poles
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Telophase II: Chromosomes decondense, nuclear membrane reforms, cells divide (cytokinesis) resulting in four haploid daughter cells
Summary ■
Meiosis is the division of a cell to form four haploid gametes, all of which may be genetically distinct if recombination occurs in prophase I
Overview of Meiosis
10.1.2 Outline the formation of chiasmata in the process of crossing over ■
Crossing over involves the exchange of segments of DNA between homologous chromosomes during Prophase I of meiosis
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The process of crossing over occurs as follows:
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Homologous chromosomes become connected in a process called synapsis, forming a bivalent (or tetrad) ■ Non-‐sister chromatids break and r ecombine with their homologous partner, effectively exchanging genetic material (crossing over) ■ The non-‐sister chromatids r emain connected in an X-‐shaped structure and the positions of attachment are called chiasmata Chiasma hold homologous chromosomes together as a bivalent until anaphase I
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As a result of crossing over, chromatids may consist of a combination of DNA derived
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from both homologues -‐ these are called recombinants Crossing Over in Prophase I
10.1.3 Explain how meiosis results in an effectively infinite genetic variety in gametes through crossing over in prophase I and random orientation in metaphase I
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During anaphase I, homologous chromosomes separate, such that each resultant daughter cell (and subsequent gametes) contains a chromosome of either maternal or paternal origin
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The orientation of these homologues in metaphase I is random, such that there is an equal probability of the daughter cell having either the maternal or paternal chromosome
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As humans have a haploid number of 23 chromosomes, this means that there is 223 potential gamete combinations (over 8 million combinations)
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Crossing over in prophase I results in entirely new chromosome combinations, as recombination through gene exchange produces wholly original chromosomes containing both maternal and paternal DNA, resulting in near infinite genetic variability
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Other sources of genetic variation include random fertilisations, DNA mutations, chromosome mutations and non-‐disjunction
10.1.4 State Mendel's law of independent assortment Gregor Mendel was a 19th century Moravian monk who demonstrated that the inheritence of traits (i.e. genes) followed particular laws: ■
Law of Segregation: Each hereditary characteristic is controlled by two alleles, which segregate and pass into different reproductive cells (gametes)
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Law of Independent Assortment: The separation of alleles for one gene will occur independently of the separation of alleles for another gene ■ ■
According to the law of independent assortment, different allele combinations should always be equally possible However this law only holds for genes that are on different chromosomes -‐ the law of independent assortment does not apply to linked genes
10.1.5 Explain the relationship between Mendel's law of independent assortment and meiosis
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The law of independent assortment relates to the random orientation of homologous chromosomes in metaphase I of meiosis
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Because the orientation of a homologous pair is random, and does not affect the orientation of any other homologous pair, any one of a pair of alleles on a chromosome has an equal chance of being paired with, or separated from, any one of a pair of alleles on another chromosome
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This means the inheritance of two different traits will occur independently of each other (provided the genes aren't linked)
Linked versus Unlinked Genes
10.2.1 Calculate and predict the genotypic and phenotypic ratio of offspring of dihybrid crosses involving unlinked autosomal genes A dihybrid cross determines the allele combinations of offspring for two particular genes that are unlinked (not on the same chromosome) Because there are two genes with two alleles per gene (multiple alleles not required), there can be up to four different gamete combinations To work out gamete combinations remember FOIL: • First (AaBb = AB) • Outside (AaBb = Ab) • Inside (AaBb = aB) • Last (AaBb = ab) When calculating genotype, always pair alleles from the same gene (e.g. ABab should be AaBb) and always write capitals first Calculating genotypic and phenotypic ratios from a dihybrid cross
10.2.2 Distinguish between autosomes and sex chromosomes Autosomes: Pairs of chromosomes that are identical in appearance (e.g. same size, same gene loci, etc.) and are not involved in sex determination Sex chromosomes: Pairs of chromosomes involved in sex determination and are not identical in appearance (e.g. X and Y chromosome in humans) 10.2.3 Explain how crossing over between non-‐sister chromatids of a homologous pair in prophase I can result in the exchange of alleles ■
During crossing over in prophase I, non-‐sister chromatids of a homologous pair may break and reform at points of attachment called chiasmata
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As these chromatids break at the same point, any gene loci below the point of the break will be exchanged as a result of recombination
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This means that maternal and paternal alleles may be exchanged between the maternal and paternal chromosomes, creating new gene combinations
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The further apart two gene loci are on a chromosome, the more likely they are to be exchanged
The Formation of Recombinant Chromosomes via Crossing Over
10.2.4 Define linkage group ■
A linkage group is a group of genes whose loci are on the same chromosome and therefore do not follow the law of independent assortment
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Linked genes will tend to be inherited together -‐ the only way to separate them is through recombination (via crossing over during synapsis)
10.2.5 Explain an example of a cross between two linked genes ■
When two genes are linked, they do not follow the expected phenotypic ratio for a dihybrid cross between heterozygous parents
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Instead the phenotypic ratio will follow that of a monohybrid cross as the two genes are inherited together
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This means that offspring will tend to produce the parental phenotypes
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Recombinant phenotypes will only be evident if crossing over occurs in prophase I and would thus be expected to appear in low numbers (if at all)
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An example of a cross between two linked genes is the mating of a grey bodied, normal wing fruit fly with a black bodied, vestigial wing mutant
Example of a Cross between Two Linked Genes 10.2.6 Identify which of the offspring are recombinants in a dihybrid cross involving linked genes Recombinants of linked genes are those combinations of genes not found in parents For example, in a test cross of a heterozygous fruit fly (grey bodied, normal wings) with a homozygous recessive mutant (black bodied, vestigial wings), the recombinants would be the grey bodied, vestigial winged offsprings and the black bodied, normal winged offspring
Linked genes that have undergone recombination can be distinguished from unlinked genes via a test cross because the frequency of the recombinant genotypes will always be less than would occur for unlinked genes (crossing over does not happen every time) ■
For example: ■ ■
Heterozygous test cross of unlinked genes = 1 : 1 : 1 : 1 phenotypic ratio Heterozygous test cross of linked genes = 1 : 1 : 0.1 : 01 phenotypic ratio (uncommon phenotypes are recombinants)
Recombination in Linked Genes 10.3.1 Define polygenic inheritance ■
Polygenic inheritance refers to a single characteristic that is controlled by more than two genes (also called multifactorial inheritance)
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Polygenic inheritance patterns normally follow a normal (bell-‐shaped) distribution curve -‐ it shows continuous variation
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By increasing the number of genes controlling a trait, the number of phenotype combinations also increase, until the number of phenotypes to which an individual can be assigned are no longer discrete, but continuous
10.3.2 Explain that polygenic inheritance can contribute to continuous variation using two examples, one of which must be human skin colour Human Skin Colour ■
The colour of human skin is determined by the amount of dark pigment (melanin) it contains
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At least four (possibly more) genes are involved in melanin production; for each gene one allele codes for melanin production, the other does not
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The combination of melanin producing alleles determines the degree of pigmentation, leading to continuous variation TED Talks: Inheritance of Human Skin Colour
Grain Colour in W heat ■
Wheat grains vary in colour from white to dark red, depending on the amount of red pigment they contain
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Three genes control the colour and each gene has two alleles (one coding for red pigment, the other coding for no pigment)
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The most frequent combinations have an equal number of 'pigment producing' and 'no pigment' alleles, whereas combinations of one extreme or the other are relatively rare
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The overal pattern of inheritance shows continuous variation
Polygenic Inheritance of Grain Wheat Colour
Sources used: -‐ Bioninjia for IB obejectives -‐ http://reviewgamezone.com/mc/candidate/test/?test_id=9393&title=Genetics%20SL%20%20 HL for multiple choice
