Chapter 15 The Chromosomal Basis of Inheritance Timeline

Chapter 15: The Chromosomal Basis of Inheritance

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

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

Morgan l l Chose to use fruit flies as a test organism in genetics. Allowed the first tracing of traits to specific chromosomes.

Fruit Fly l l Drosophila melanogaster Early test organism for genetic studies.

Life Cycle l l Egg Larva Pupa Adult

Reasons l l l Small Cheap to house and feed Short generation time Many offspring Few chromosomes

Fruit Fly Chromosomes

Genetic Symbols l Mendel - use of uppercase or lowercase letters. T = tall t = short l Morgan: symbol from the mutant phenotype. + = wild phenotype

Examples l Recessive mutation: l l l w = white eyes w+ = red eyes Dominant Mutation l Cy = Curly wings l Cy+ = Normal wings

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

Morgan crossed l The white eye male with a normal red eye female.

The F 1 offspring: l l l All had red eyes. This suggests that white eyes is a genetic _____? Recessive.

F 1 X F 1 = F 2 l l l Morgan expected the F 2 to have a 3: 1 ratio 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: l l Sex linked traits. Genetic traits whose expression are dependent on the sex of the individual.

Fruit Fly Chromosomes

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

Linked Genes l l Traits that are located on the same chromosome. Result: l l 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 ratio. If linked: ratio will be altered.

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

If Genes are Linked: l l Independent Assortment of traits fails. Linkage may be “strong” or “weak”.

Linkage Strength l Degree of strength related to how close the traits are on the chromosome. l l Weak - farther apart Strong - closer together

Genetic Maps l l Constructed from crossing-over frequencies. 1 map unit = 1% recombination frequency.

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

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

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

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

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

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

Sex Linkage l l l Inheritance of traits on the sex chromosomes. X- Linkage (common) Y- Linkage (rare)

Males l l l 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 l l l Color blindness Duchenne's Muscular Dystrophy Hemophilia (types a and b)

Samples of X-linked patterns:

X-linked Patterns l l 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 l l l Watch how questions with sex linkage are phrased: Chance of children? Chance of males?

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

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

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

Sex Influenced Traits l l Traits whose expression differs because of the hormones of the sex. Ex. – beards, mammary gland development, baldness

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

Lyon Hypothesis l l l 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 l l Calico Cats. Human examples are known such as a sweat gland disorder.

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

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

Chromosomal Alterations l l Changes in number. Changes in structure.

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

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

Comment l l Nondisjunction in Meiosis I produces 4 abnormal gametes. Nondisjunction in Meiosis II produces 2 normal and 2 abnormal gametes.

Types of Aneuoploidy l l Monosomy: 2 N – 1 (very rare) Trisomy: 2 N + 1 (more common)

Turner Syndrome l l 2 N - 1 or 45 chromosomes Genotype: X_ or X 0. Phenotype: female, but very poor secondary sexual development.

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

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

Other Sex Chromosome changes l l l Kleinfelter Syndrome Meta female Supermale

Kleinfelter Syndrome l l 2 N + 1 (2 N + 2, 2 N + 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

George Washington l l l May have been a Kleinfelter Syndrome individual. Much taller than average. Produced no children.

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

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

Trisomy events l l l Trisomy 21: Downs Syndrome Trisomy 13: Patau Syndrome Both have various physical and mental changes.

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

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

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

Question? l l 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 l l Deletions Duplications Inversions Translocations

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

Translocations

Cri Du Chat Syndrome l l Part of p arm of #5 missing. Good survival. Severe mental retardation. Small sized heads common.

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

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

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

Cause: l Imprints are "erased" in gamete producing cells and re-coded by the body according to its sex.

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

Why have parental imprinting? l Method to detect that TWO different sets of chromosomes are in the zygote.

Experiment l l Can fuse nuclei into mouse eggs. If male/male = normal placenta, abnormal fetus If female/female = abnormal placenta, normal fetus If male/female = normal placenta and normal fetus

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

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

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

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

Variegated Examples

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

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

Summary l Be able to work genetics problems for this chapter.