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 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.

Life Cycle Egg Larva Pupa Adult

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

Fruit Fly Chromosomes

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

Examples 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.

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

F 1 X F 1 = F 2 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: Sex linked traits. Genetic traits whose expression are dependent on the sex of the individual.

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.

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

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

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

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

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

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

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.

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 surface receptor.

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

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)

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 factors 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 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. Human examples are known such as a sweat gland disorder.

Calico Cats X B = black fur X O = orange fur Calico is heterozygous, X B X O.

Question? Why don’t you find many calico males? They must be X B X O Y 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.

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

Comment 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 Meta female Supermale

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

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

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: 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.

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

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

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.

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.

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.

Experiment 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 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.

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.

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

Variegated Examples

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. Variations of chromosomes and inheritance patterns.

Summary Be able to work genetics problems for this chapter.