CHAPTER 11 & 12

Mendel & the Gene Idea & the Chromosomal Basis of Inheritance

Genetics • study of science of heredity • began w/the use of wild type traits – traits most commonly found in nature • desirable traits were then bred

Con. 11.1

Mendel’s Methods

• used true breeding plant – made by self-

fertilization • created hybrids by cross-fertilization (crossing 2 different true breeding plants) - P generation is parent generation

- F1 generation (1st filial) is offspring of P generation - F2 generation (2nd filial) is offspring made by F1 x F1

Mendel’s Principles (Principle of Segregation)

1. alternative forms for genes called alleles (DNA sequence variations) 2. an organism has 2 genes (alleles): 1 inherited from each parent - sperm & egg each carry only 1 allele for each inherited characteristic

3. when the alleles of the pair are different, 1 is fully expressed, the other is masked - dominant allele is expressed - recessive allele is masked 4. Law of Segregation states that the allele pairs separate during gamete formation (meiosis) & restored during fertilization

Punnett Square – diagram used to predict results of a genetic cross

Homozygous – identical alleles for a trait ex: G = green GG g = yellow gg Heterozygous – 2 different alleles for a trait Gg

Phenotype – the expressed trait (physical appearance green or yellow) Genotype – organism’s genetic makeup (GG, Gg, gg)

Mendel’s Principles

(Independent Assortment) • Monohybrid Cross – parents differ only in a single trait Pod Color G = green g = yellow Genotype: 50% Gg & 50% gg Phenotype: 50% green & 50% yellow

•Dihybrid Cross – parents differ in 2 different traits

- it follows the law of independent assortment - each allele pair separates independently during gamete formation P generation: RRYY x rryy

Pea Shape R=round r=wrinkled Pea Color Y=yellow y=green Gametes RY x ry RrYy F 1: RrYy x RrYy

Gametes: F2

Genotype

Phenotype

•Testcross – a breeding of the recessive homozygote w/an organism of unknown genotype Practice a testcross

Con. 11.3

Complications of Genotypes to Phenotypes

Incomplete Dominance – when 1 allele is not dominant over the other (snapdragon) Multiple Alleles – some genes exist in more than 2 allele forms: blood types - A, B, AB, O (phenotypes) - A & B are codominant

Incomplete Dominance RR=red WW=white RW=pink

RR x WW

F2 RW x RW G

P

Pleiotropy – when a gene has multiple effects

- affects phenotypic characteristics Ex: sickle-cell anemia (single recessive allele on both homologues) causes formation of abnormal hemoglobin which in turn causes: breakdown of red blood cells, clumping of cells & clogging of small blood vessels, accumulation of sickle cells in spleen

NOTE: each of these causes additional effects on an individual

-individuals who are heterozygous are called carriers because they “carry” the disease-causing allele & may transmit it to their offspring Epistasis (p. 217) – one gene dictates the phenotypic expression of another

Polygenic Inheritance – an additive of 2 or more genes on a single phenotypic characteristic (skin color controlled by at least 3 genes) p. 218 Phenotypic range – norm of reaction (diet vs. genetics): multifactional

Quantitative Characters – gradations along a continuum

Chromosomal Theory of Inheritance • Mendelian genes are located on chromosomes • Chromosomes undergo segregation & independent assortment Ch. 12

Linked Genes • Discovered in 1908 by William Bateson & Reginald Punnett • Found on same chromosome • The principle of independent assortment does not apply because the genes are part of a single chromosome…p. 236

Chromosomal Basis of Recombination • Genetic Recombination – production of offspring that combine the traits of 2 parents • In unlinked genes independent assortment will take place - parental types – offspring w/same phenotype as one or the other of the parents Con. 12.2

- Recombinants – offspring having different combinations than either parent Linked Genes – independent assortment does not take place - crossing over can occur so new combinations are passed on - recombination does occur

Mapping Chromosomes Cross Over Data Relative Distance Between Genes • Use recombination • Determined by crossover data to assign a frequency position to genes • The greater the • A map unit is equal distance between to 1% genes, the greater recombination the chance for frequency crossing over to occur

Chromosomal Basis of Sex Determination • Humans & other mammals have XX & XY • Most insects have XX (female) & XO (male) • Birds, fish, butterflies, moths have a ZW system: ZW (female and determines sex) & ZZ (male) • Most bees & ants are haplo-diploid: female from fertilized eggs (diploid), male from unfertilized eggs (haploid) – parthenogenesis – virgin birth

NOTE: not all organisms have separate sexes -plants are monoecious (one house), ex: corn - animals are hermaphroditic – all individuals of a species have the same compliment of chromosomes ex: earthworms, garden snails

Morgan: Sex Linkage • Worked w/fruit flies –

Drosophlia

- found that the gene for eye

color is on the X chromosome: R = red r = white - mated white eyed male w/red eyed female (wild) * all F1 have red eyes, then mated F1 x F1 p. 230

XRXR x XrY Xr

Y

G

P

G

P

XR

XR F2

XR Xr

XR

Y

The human genome project is: a.The main character in Travelocity commercials b.Yard art c. Aimed at sequencing all the DNA on the human chromosomes

Genome

• One complete haploid set of chromosomes of an organism • in humans, 23 chromosomes w/approximately 3 billion nucleotide pairs of DNA that carry between 50,000 & 100,000 genes •If genome’s chromosomes were uncoiled and laid end to end, they would make a very thin thread that would be approximately 3 meters long

Karyotype • A photographic overview of a person’s genome • cells from a person are fixed in metaphase, stained, & photographed to display all of a cell’s chromosomes

• Individual chromosomes are cut out, paired w/their homologue, & arranged from largest to smallest pairs for the 22 autosomes w/the sex chromosomes placed last

• the karyotype is used to screen for abnormal numbers of chromosomes or defective chromosomes

p. 240

Major Chromosomal Alterations & Their Effects Chromosome Numbers

• nondisjunction - when chromosomes fail to separate during Meiosis I and II • can cause aneuploidy - abnormal chromosome numbers: * monosomy (1 less chromosome) * trisomy (1 extra chromosome)

Human Disorders

(nondisjunction/aneuploidy) 1. Down Syndrome - trisomy on chromosome #21 *occurs in 1 of every 700 births *rounded facial features, varying degrees of mental delays p. 242

2. Patau Syndrome - trisomy on chromosome #13 *occurs in 1 of every 5000 births *causes cleft palate, harelip, brain defects #13

3. Edwards Syndrome - trisomy on chromosome #18 *occurs in 1 of every 10,000 births *affects almost every organ system

4. Klinefelter Syndrome - trisomy in male (XXY) *occurs in 1 of every 2000 births *has male sex organs but are sterile

5. Metafemale - trisomy in female (XXX) *occurs in 1 of every 1000 births *limited fertility but otherwise appear normal

6. Turner Syndrome - monosomy in female (XO) *occurs in 1 of every 5000 births *no mature sex organs, sterile

Chromosome Structure

• Breakage of a chromosome can cause a variety of rearrangements • fragments are usually lost when a cell divides in 1 of 4 ways: p. 241

1-DELETION = a fragment of the

chromosome breaks off and is lost (only dealing with one homologue)

For example, in this picture gene 3 has broken off and been lost.

becomes

(Where did gene 3 run off to?)

2-DUPLICATION = chromosome fragment attaches to a homologue now one homologue has 2 sets of (same) info. and the other is missing info. (Old Homologue 2) OLD {12}345678 (Homologue 1 is left 12345678 without genes 1 & 2. Homologue 2 ends NEW up with both copies 345678 of genes #1 & 2.) 12{12}345678 (New Homologue 2)

3-INVERSION = chromosome breaks off and reattaches in reverse order (only dealing with one homologue) {234} Becomes {432}

4-TRANSLOCATION = a fragment

breaks off and attaches to a nonhomologue (Example – chromosome 1 has a piece break off Chromo.#1 and attach to chromosome number 2 which is a Chromo. #2 non-homologue) (What will the new chromosome #1 look like?)

345678

New #2

Example of deletion: Williams Syndrome – deletion of about 15 genes on 1 of the homologous chromosomes in chromosome #7 *occurs in 1 of every 20,000 births *mild retardation, problems in grasping spatial relationships; possess extraordinary musical talent *thought to be elves/pixies in medieval folklore

Inherited Disorders Due to Gene p. 220-222 Mutations Human Pedigree - a pedigree shows the occurrence of a trait, seen in a family tree type of style Recessively Inherited Disorders carrier - a heterozygote (Xx) that is phenotypically normal but transmits the recessive allele to the offspring

1. Deafness - severely or totally deaf Dd = carrier (normal) DD = normal dd = deaf

2. Cystic Fibrosis - excessive mucus secretions clog airways of lungs & passages of the liver and pancreas

3. Albinism - lack of (skin) pigmentation 4. Tay-Sachs - an incurable disorder in which the brain deteriorates due to lipid build-up (p. 216) 5. Sickle Cell Anemia - red blood cells are defective so they don’t transport O2 tissues properly (caused by point mutation)

Dominantly Inherited Disorders 1. Dwarfism (Achondroplasia)homozygous dominant results in spontaneous abortion 2. Alzheimer’s Disease-causes mental deterioration (normally no obvious effect until late in life and effects are irreversible and lethal)

3. Huntington’s Disease - degenerative disorder of the brain cells

*no obvious effect until after age 30 *effects are irreversible and lethal Why are Alzheimer’s and Huntington’s becoming so common?

Sex Linked Traits - fathers pass X linked traits on to all of their daughters and mothers can pass sex linked traits on to both sons and daughters Examples: Hemophilia - blood disorder passed from generation to generation p. 232-233

Color Blindness - inability to see certain colors due to malfunctioning lightsensitive cells in the eyes Duchenne Muscular Dystrophy progressive weakening and loss of muscle tissue X inactivation in female mammals due to DNA methylation p. 233

Risk Assessment and Therapy for Genetic Disorders • Fetal Testing Amniocentesis - needle obtains small sample of amniotic fluid *culture cells are taken from sloughed off cell floating in amniotic fluid p. 223

*done around 14-16 weeks of pregnancy *karyotype performed *results in several weeks (risk to pregnancy - 1%)

Chorionic Villus Sampling (CVS) - small tube suctions off a small amount of tissue from the villi of the embryonic membrane (this tissue forms part of the placenta) *cells are rapidly undergoing mitosis *done around 8-10 weeks of pregnancy *perform a karyotype *results in 1 day (risk to pregnancy 2%)

Ultrasound Imaging - high frequency sound waves (sonar beyond the range of hearing) *produces a colorenhanced image of fetus - age 18 weeks on *results are immediate (noninvasive and no known risk) *used during amniocentesis and CVS to determine position of fetus and needle or tube

Fetoscopy - needle thin tube w/viewing lens & light source *produces direct view of fetus *results are immediate (risk to pregnancy - 10%) - risks to pregnancy can be complications that can result in maternal bleeding, miscarriage, or premature birth

• Carrier Recognition Counseling Problem: parents are concerned they are carrier of a recessive genetic disorder; they do not wish to pass the disorder onto their prospective children Solution: physicians and genetic counselors now have a growing list of relatively simple biochemical tests that can check a couple’s genotype for genetic disorders

• Identification of Defective Genes and Gene Therapy

- work by Dr. Nancy Wexler on Huntington’s Disease as well as ongoing research making progress in locating defective genes - her work in Venezuela produced a pedigree linking almost 10,000 people

- this allowed her to find a genetic marker (a DNA strand signaling the presence of a specific allele) and a test to identify for HD in 1983 - she located the HD allele in 1993 and identified the allele’s operation - set up gene therapy

Problems w/gene therapy: Technical - new gene must work at the right time and throughout life, and gene therapy works only with cells that currently multiply (nerve cells do not) Ethical - who will have access to it, treat only serious diseases, enhance athletic ability/physical appearance, and treatment of germ cells (makes gametes)

www.biology.ewu.edu/. ../ GeneTherapyTargeted.jpg

Human Genome Project • Purpose: map all 3 billion nucleotides (international, multi-billion, multidecade long successful effort) • Potential: insight & understanding into embryonic development & evolution, aid in diagnosis, treatment, prevention of many diseases

Yeast & Fly Genomes • Reproduces by budding and doubles every 90 minutes • sequenced in 1996 • 12 million base pairs of DNA • 6000 genes, at least 31% have human equivalents

• Lifespan 2-3 months, new generation every 10 days • sequenced in March 2000 • 165 million base pairs of DNA • 13,600 genes, 50% have human equivalents

Mouse & Human Genome • Lifespan 2 years, new generation every 9 weeks • sequenced in 2001 • 3 billion base pairs of DNA • 40,000 genes • equivalents to human and some blocks proved impossible to tell apart from human

• Lifespan in U.S. 70-80 years, new generation every 20-25 years • preliminary draft in June 2000 • Close to final draft in 2004 • 3 billion base pairs of DNA • 50,000 genes

Ethical Issues • Who has access to your genome? • How far, if at all, do we go to re-engineer someone? • How do we prevent genetic discrimination in the workplace, insurance companies, social settings, etc.?