Chapter 15 The Chromosomal Basis of Inheritance

Timeline 1866- Mendel's Paper 1875- Mitosis worked out 1890's- Meiosis worked out 1902- Sutton, Boveri et. al. connect chromosomes to Meiosis.

Parents are two true-breeding pea plants Parent 1 Yellow, round Seeds (YYRR) Parent 2 Green, wrinkled seeds (yyrr) These 2 genes are on different chromosomes. Draw meiosis to determine the resulting gametes of parent 1. How do the resulting gametes connect to Punnett squares?

What are the predicted phenotypic ratios of the offspring? F1: YyRr x YyRr What are the predicted phenotypic ratios of the offspring? ¾ yellow ¾ round ¼ green ¼ wrinkled ¼ (green) x ¼ (wrinkled) = 1/16 green, wrinkled 9:3:3:1 phenotypic ratio

First Experimental Evidence to connect Mendelism to the chromosome Thomas Morgan (1910) Chose to use fruit flies as a test organism in genetics. Allowed the first tracing of traits to specific chromosomes.

Fruit Fly Drosophila melanogaster Early test organism for genetic studies.

Reasons Small Cheap to house and feed Short generation time Many offspring 3 pairs of Autosomes 1 pair of sex chromosomes

Examples Wild type is most common, NOT dominant or recessive Recessive mutation: w = white eyes w+ = red eyes Dominant Mutation Cy = Curly wings Cy+ = Normal wings

Morgan Observed: A male fly with a mutation for white eyes.

Morgan crossed The white eye male with a normal red eye female. Male ww x Female w+w+

The F1 offspring: All had red eyes. This suggests that white eyes is a _________? Recessive. F1= w+w What is the predicted phenotypic ratio for the F2 generation?

F1 X F1 = F2 Expected F2 ratio - 3:1 of red:white He got this ratio, however, all of the white eyed flies were MALE. Therefore, the eye color trait appeared to be linked to sex.

Morgan discovered: Sex linked traits. Genetic traits whose gene are located on the sex chromosome

Female Male XX XY Fruit Fly Chromosomes Presence of Y chromosome determines the sex Just like in humans!

Morgan Discovered There are many genes, but only a few chromosomes. Therefore, each chromosome must carry a number of genes together as a “package”.

Sex-Linked Problem A man with hemophilia (a recessive, sex-linked, x-chromosome condition) has a daughter of normal phenotype. She marries a man who is normal for the trait. A. What is the probability that a daughter of this mating will be a hemophiliac? B. That a son will be a hemophiliac? C. If the couple has four sons, what is the probability that all four will be born with hemophilia?

Original Man - XhY Daughter - must get the dad’s X chromosome XHXh (normal phenotype, so she’s a carrier) Daughter’s husband XHY (normal phenotype) A. daughter must get XH from the dad. 0% (50% carrier, 50% homo dom.) B. son must get Y from dad. 50% chance to be hemophiliac C. ½ x ½ x ½ x ½ = 1/16

Linked Genes Traits that are located on the same chromosome. Result: Failure of Mendel's Law of Independent Assortment. Ratios are different from the expected

Example: Body Color - gray dominant Wing Type - normal dominant b+ - Gray b - black Wing Type - normal dominant vg+ - normal vg – vestigial (short)

b+b vg+vg X bb vgvg Predict the phenotypic ratio of the offspring Example b+b vg+vg X bb vgvg Predict the phenotypic ratio of the offspring

Show at board b+b x bb vg+vg x vgvg ½ gray ½ black ½ normal ½ vestigial -----------------------------------------------------¼ gray normal, ¼ gray vestigial, ¼ black normal, ¼ black vestigial 1:1:1:1 phenotypic ratio

Conclusion Most offspring had the parental phenotype. Both genes are on the same chromosome. What do you expect to happen if they’re on the same chromosome? (draw chromosomes) bbvgvg parent can only pass on b vg b+b vg+vg can pass on b+ vg+ or b vg

b+b vg+vg - Chromosomes (linked genes)

Crossing-Over Breaks up linkages and creates new ones. Recombinant offspring formed that doesn't match the parental types. Higher recombinant frequency = genes further apart on chromosome

If Genes are Linked: Independent Assortment of traits fails. Linkage may be “strong” or “weak”. Strong Linkage means that 2 alleles are often inherited together.

Degree of strength related to how close the traits are on the chromosome.

Genetic Maps Constructed from crossing-over frequencies. 1 map unit = 1% recombination frequency. Can use recombination rates to ‘map’ chromosomes.

Comment - only good for genes that are within 50 map units of each other. Why? Over 50% gives the same phenotypic ratios as genes on separate chromosomes

Genetic Maps Have been constructed for many traits in fruit flies, humans and other organisms.

Sex Linkage in Biology Several systems are known: Mammals – XY and XX Diploid insects – X and XX Birds – ZZ and ZW Social insects – haploid and diploid

Chromosomal Basis of Sex in Humans X chromosome - medium sized chromosome with a large number of traits. Y chromosome - much smaller chromosome with only a few traits.

Human Chromosome Sex Males - XY Females - XX Comment - The X and Y chromosomes are a homologous pair, but only for a small region at one tip.

SRY Sex-determining Region Y chromosome gene. If present - male If absent - female SRY codes for a cell receptor.

Sex Linkage Inheritance of traits on the sex chromosomes. X- Linkage (common) Y- Linkage (very rare if exists at all)

Males Hemizygous - 1 copy of X chromosome. Show ALL X traits (dominant or recessive). More likely to show X recessive gene problems than females.

X-linked Disorders Color blindness Duchenne's Muscular Dystrophy Hemophilia (types a and b) Immune system defects

Samples of X-linked patterns:

X-linked Patterns Trait is usually passed from a carrier mother to 1/2 of sons. Affected father has no affected children, but passes the trait on to all daughters who will be carriers for the trait.

Comment Watch how questions with sex linkage are phrased: Chance of children? Chance of males?

Can Females be color-blind? Yes, if their mother was a carrier and their father is affected.

Y-linkage Hairy ear pinnae. Comment - new techniques have found a number of Y-linked markers that can be shown to run in the males of a family. Ex: Jewish priests

Sex Limited Traits Traits that are only expressed in one sex. Ex – prostate

Sex Influenced Traits Traits whose expression differs because of the hormones of the sex. These are NOT on the sex chromosomes. Ex. – beards, mammary gland development, baldness

Baldness Testosterone – the trait act as a dominant. No testosterone – the trait act as a recessive. Males – have gene = bald Females – must be homozygous to have thin hair.

Barr Body Inactive X chromosome observed in the nucleus. Way of determining genetic sex without doing a karyotype.

Lyon Hypothesis Which X inactivated is random. Inactivation happens early in embryo development by adding CH3 groups to the DNA. Result - body cells are a mosaic of X types.

Examples Calico Cats. Human examples are known such as a sweat gland disorder.

Calico Cats XB = black fur XO = orange fur Calico is heterozygous, XB XO.

Question? Why don’t you find many calico males? They must be XB XOY and are sterile.

Chromosomal Alterations Changes in number. Changes in structure.

Number Alterations Aneuploidy - too many or too few chromosomes, but not a whole “set” change. Polyploidy - changes in whole “sets” of chromosomes.

Nondisjunction When chromosomes fail to separate during meiosis Result – cells have too many or too few chromosomes which is known as aneuploidy

Meiosis I vs Meiosis II Meiosis I – all 4 cells are abnormal Meiosis II – only 2 cells are abnormal

Aneuploidy Caused by nondisjunction, the failure of a pair of chromosomes to separate during meiosis.

Types Monosomy: 2N - 1 Trisomy: 2N + 1

Turner Syndrome 2N - 1 or 45 chromosomes Genotype: X_ or X0. Phenotype: female, but very poor secondary sexual development.

Characteristics Short stature. Extra skin on neck. Broad chest. Usually sterile Normal mental development except for some spatial problems.

Question Why are Turner Individuals usually sterile? Odd chromosome number. Two X chromosomes need for ovary development.

Homework Read Chapter 15 (Hillis – 8) Genetics Lab Report – today No class Feb. 4 and 5 Chapter 15 – Thurs. 2/7

Other Sex Chromosome changes Kleinfelter Syndrome Meta female Supermale

Kleinfelter Syndrome 2N + 1 Genotype: XXY Phenotype: male, but sexual development may be poor. Often taller than average, mental development fine, usually sterile.

Meta female 2N + 1 or 2N + 2 Genotype: XXX or XXXX Phenotype: female, but sexual development poor. Mental impairment common.

Super male 2N + 1 or 2N + 2 Genotype: XYY or XYYY Phenotype: male, usually normal, fertile.

Trisomy events Trisomy 21: Down's Syndrome Trisomy 13: Patau Syndrome Both have various physical and mental changes.

Question? Why is trisomy more common than monosomy? Fetus can survive an extra copy of a chromosome, but being hemizygous is usually fatal.

Question? Why is trisomy 21 more common in older mothers? Maternal age increases risk of nondisjunction.

Polyploid Triploid= 3N Tetraploid= 4N Usually fatal in animals.

Question? In plants, even # polyploids are often fertile, why odd # polyploids are sterile. Why? Odd number of chromosomes can’t be split during meiosis to make spores.

Structure Alterations Deletions Duplications Inversions Translocations

Translocations

Result Loss of genetic information. Position effects: a gene's expression is influenced by its location to other genes.

Cri Du Chat Syndrome Part of p arm of #5 missing. Good survival, but low birth weight and slow gain. Severe mental impairment. Small sized heads common.

Cri Du Chat Syndrome

Philadelphia Chromosome An abnormal chromosome produced by an exchange of portions of chromosomes 9 and 22. Causes chronic myeloid leukemia.

Parental Imprinting of Genes Gene expression and inheritance depends on which parent passed on the gene. Usually caused by different methylations of the DNA.

Example: Prader-Willi Syndrome and Angelman Syndrome Both lack a small gene region from chromosome 15. Male imprint: Prader-Willi Female imprint: Angelman

Cause: Imprints are "erased" in gamete producing cells and re-coded by the body according to its sex. Gametes are methylated to code as “male “ or “female”.

Result Phenotypes don't follow Mendelian Inheritance patterns because the sex of the parent does matter.

Extranuclear Inheritance Inheritance of genes not located on the nuclear DNA. DNA in organelles. Mitochondria Chloroplasts

Result Mendelian inheritance patterns fail. Maternal Inheritance of traits where the trait is passed directly through the egg to the offspring.

Chloroplasts Gives non-green areas in leaves, called variegation. Several different types known. Very common in ornamental plants.

Variegation in African Violets

Variegated Examples

Mitochondria Myoclonic Epilepsy Ragged Red-fiber Disease Leber’s Optic Neuropathy All are associated with ATP generation problems and affect organs with high ATP demands.

Comment Cells can have a mixture of normal and abnormal organelles. Result - degree of expression of the maternal inherited trait can vary widely.

Summary Know about linkage and crossing-over. Sex chromosomes and their pattern of inheritance.

Summary Be able to work genetics problems for this chapter.