Extra credit problem for Lecture #4

An agouti mouse is crossed to a white mouse and all the F1 offspring are agouti.

An F1 female is crossed to an F1 male, and the offspring are:

11 agouti: 5 white: 4 black

Q: Test the hypothesis that the original parental genotypes were BBCC and bbcc. Give the 2 value, the df, the P value, and state whether or not you reject the hypothesis.

Cytogenetics: Chromosome Mutations, Aberrations &

Evolution

Chromosomes

Prokaryote Eukaryote4.2 X 106 base pairs Has 1000x more DNADNA essentially naked DNA complexed w/ RNA & proteinmRNA translated as mRNA is transcribed in nucleus, it's transcribed translated in the cytoplasmmRNA is often polycistronic mRNA is almost never

polycistronic

Eukaryotic chromosomes

Metacentric Submetacentric Acrocentric

Human karyotype

Homologous pair

Sex chromosomesautosomes

Sister chromatids

Why do we care?

Many diseases and birth defects are a direct result of missing, broken, or extra chromosomes.

• Down Syndrome

• Cri du chat Syndrome

• Patau Syndrome

Mutations at the level of the homologous pair

• EUPLOIDY: "true" ploidy, meaning two members of each homologous pair.

• ANEUPLOIDY: "not true" ploidy, meaning more or fewer members than two of each homologous pair.

• MONOSOMY - one homolog; partner is missing

• TRISOMY - three homologs• NULLISOMY- one entire homologous pair is

missing.

Monosomy and Trisomy

Down Syndrome

How does it happen? Nondisjunction

Each chrom.has twochromatids

Trisomy: Patau Syndrome

• 1/20,000 births

• severe mental retardation

• heart and organ defects

• polydactyly

• death by the age of one year

Chromosomal Abnormalities Occurring in Human Fetuses

Type of Abnormality

% spontaneously abortedfetuses with the

abnormality

% fetuses with theabnormality thatsurvive to term

All abnormalities 50 5Autosomal Trisomies 16 7.5 0 13, 18, & 21 4.5 15 All others 13.8 0Trisomies of Sex chromosomesXXX, XXY, XYY 0.3 75Monosomy for X (XO) 8.7 1Structural Abnormalities 20 45

Structural Changes

• Deletions (deficiencies)

• Duplications

• Inversions

• Translocations

w

Psuedo-dominanceHomozygotes

lethal

Deletions (deficiencies)

How can chromosomes break?

Ionizing radiation (production of free radicals, which act like little atomic "cannon balls", blasting through strands of DNA or c'somes.

Chemical insult.

Break points of chromosomes are highly reactive ("sticky"), whereas normal ends of c'somes are capped by telomeres, which do not readily bond to other molecules.

Why do they rejoin?

• Breaks that occur before S phase will affect both newly formed chromatids, & all daughter cells arising from them.

• Breaks that occur when the chromosome is in dyad form may affect only one chromatid. (Thereafter, only the progeny carrying the broken chromatid will be affected.)

S Phase

Dyad

Cri-du-chat Syndrome1/50,000 birthsDeletion short arm chrom 5Mental retardationSlow motor skill

developmentLow birth weight and slow

growthSmall head (microcephaly)Partial webbing of fingers or

toesWide-set eyes

(hypertelorism)High-pitched cry

Structural Changes

• Deletions (deficiencies)

• Duplications

• Inversions

• Translocations

Duplication is a source of new genes over evolutionary time:e.g., gene families like globins and MHC genes

Duplications

Bar eye: caused by duplication

Duplications: source of evolutionary novelty?

• Ribosomal DNA• Globins (alpha and

beta)• Homeobox genes

Structural Changes

• Deletions (deficiencies)

• Duplications

• Inversions

• Translocations

Inversions