Chapter 15: The Chromosomal Basis of Inheritance

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

Sutton Developed the “Chromosome Theory of Inheritance”. Mendelian factors or alleles are located on chromosomes. Chromosomes segregate and show independent assortment.

Morgan Chose to use Drosophila melanogaster (fruit flies) as a test organism in genetics. Why? Small Cheap to house and feed Short generation time Many offspring Few chromosomes Allowed the first tracing of traits to specific chromosomes. Discovered sex linked traits

Life Cycle Egg Larva Pupa Adult

Genetic Symbols Mendel - use of uppercase or lowercase letters. T = tall t = short Morgan: symbol from the mutant phenotype. + = wild phenotype Recessive mutation: w = white eyes w+ = red eyes Dominant Mutation Cy = Curly wings Cy+ = Normal wings

Fruit Fly Chromosomes

Morgan Discovered There are many genes, but only a few chromosomes. Therefore, each chromosome must carry a number of genes together as a “package”. Linked Genes Traits that are located on the same chromosome. Result: Failure of Mendel's Law of Independent Assortment. Ratios mimic monohybrid crosses.

Body Color and Wing type

Example b+b vg+vg X bb vgvg (b+ linked to vg+) (b linked to vg) If unlinked: 1:1:1:1 ratio. If linked: ratio will be altered.

If Genes are Linked: Independent Assortment of traits fails. Linkage may be “strong” or “weak”. Degree of strength related to how close the traits are on the chromosome. Weak - farther apart Strong - closer together

Crossing-Over Breaks up linkages and creates new ones. Recombinant offspring formed that doesn't match the parental types.

Genetic Maps Constructed from crossing-over frequencies. 1 map unit = 1% recombination frequency. Have been constructed for many traits in fruit flies, humans and other organisms.

Comment - only good for genes that are within 50 map units of each other. Why?

Sex Linkage in Biology Several systems are known: 1. Mammals – XX and XY 2. Diploid insects – X and XX 3. Birds – ZZ and ZW

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. 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 surface receptor.

Sex Linkage Inheritance of traits on the sex chromosomes. X- Linkage (common) Color blindness Duchenne's Muscular Dystrophy Hemophilia (types a and b) Y- Linkage (rare) Hairy ear rims

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

Samples of X-linked patterns:

Traits Sex Limited Traits Traits that are only expressed in one sex. Ex – prostate glands Sex Influenced Traits Traits whose expression differs because of the hormones of the sex. Ex. – beards, mammary gland development, baldness Baldness Testosterone – makes the trait act as a dominant. No testosterone – makes 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 CH 3 groups to the DNA. Result - body cells are a mosaic of X types.

Examples Calico Cats. X B = black fur X O = orange fur Calico is heterozygous, X B X O. Why don’t you find many calico males? They must be X B X O Y and are sterile. Human examples are known such as a sweat gland disorder.

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

Aneuploidy Caused by nondisjunction, the failure of a pair of chromosomes to separate during meiosis. Nondisjunction in Meiosis I produces 4 abnormal gametes. Nondisjunction in Meiosis II produces 2 normal and 2 abnormal gametes. Types of Aneuoploidy Monosomy: 2N – 1 (very rare) Trisomy: 2N + 1 (more common)

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 needed for ovary development.

Other Sex Chromosome changes Kleinfelter Syndrome 2N + 1 (2N + 2, 2N + 3) Genotype: XXY (XXXY, XXXXY) Phenotype: male, but sexual development may be poor. Often taller than average, mental development fine (XXY), usually sterile. More X = more mental problems Meta female 2N + 1 or 2N + 2 Genotype: XXX or XXXX Phenotype: female, but sexual development poor. Mental impairment common. Supermale 2N + 1 or 2N + 2 Genotype: XYY or XYYY Phenotype: male, usually normal, fertile.

Trisomy events Trisomy 21: Downs 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. 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.

Chromosome Structure Alterations Deletions Result Loss of genetic information. Position effects: a gene's expression is influenced by its location to other genes. Duplications Inversions Translocations

Cri Du Chat Syndrome Part of p arm of #5 missing. Good survival. Severe mental retardation. Small sized heads common. 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. Imprints are "erased" in gamete producing cells and re-coded by the body according to its sex. Example: Prader-Willi Syndrome and Angelman Syndrome Both lack a small gene region from chromosome 15. Male imprint: Prader-Willi Female imprint: Angelman

Result Phenotypes don't follow Mendelian Inheritance patterns because the sex of the parent does matter. Why have parental imprinting? Method to detect that TWO different sets of chromosomes are in the zygote.

Summary Know about linkage and crossing-over. Sex chromosomes and their pattern of inheritance. Variations of chromosomes and inheritance patterns. Be able to work genetics problems for this chapter.