Chapter 15 Chromosomal Basis of Inheritance

Mendel & Chromosomes Mendel was ahead of his time. 19th C cytology suggested a mechanism for his earlier findings. What did they find? Chromosomes and genes are both present in pairs in diploid cells. Homologous chromosomes separate and alleles segregate during meiosis. Fertilization restores the paired condition for both chromosomes and genes.

Chromosome Theory of Inheritance Mendelian genes have specific loci on chromosomes Chromosomes are what physically undergo segregation and independent assortment.

Morgan first associated a specific gene with a specific chromosome. Morgan’s Fruit Flies Morgan first associated a specific gene with a specific chromosome. Why fruit flies? Breed quickly (two week generations) 4 pairs of chromosomes (3 pair of autosomes, 1 pair of sex chromosomes) Females = XX Males = XY

Wild Type flies are the most common natural phenotype. (Red Eyes) Morgan’s Fruit Flies Wild Type flies are the most common natural phenotype. (Red Eyes) After a series of crosses, Morgan produced mutants with white eyes. After a few generations, Morgan noted that only males displayed the white eyes. He concluded that certain genes are located on the sex chromosome and thus linked to sex. Sex-linked genes (ie: hemophilia)

Sex-linked Traits

Males (XY) only need one copy of recessive allele to show trait. Sex-linked Traits Morgan concluded the gene with the white-eyed mutation is on the X chromosome. Y chromosome = no info Males (XY) only need one copy of recessive allele to show trait.

Linked Genes All genes located on the same chromosome tend to be inherited together. Chromosome passed on as a unit. Testcross results varied from those predicted by the law of independent assortment. This showed that certain genes will assort together. (on same chromosome)

Linked Genes

Linked Genes Body color and wing shape are usually inherited together (same chromosome)

Recombinants Where did the other phenotypes come from? (grey-vestigial and black normal) Genetic recombination= offspring with new combinations of traits inherited from two parents How?? independent assortment of genes (non-homologous) crossing over of genes (homologous)

Recombinants Mendel’s dihybrid crosses produced recombinant genotypes. 50% parental : 50% recombinant genotypes typical for nonhomologues Metaphase I YR, Yr, yR, and yr Seed shape and color tetrads are independent from one another

Recombinants Linked genes tend to move together during meiosis/fertilization If Independent assortment of genes Expect a 1:1:1:1 phenotype ratio If Complete linkage of genes 1:1:0:0 ratio (all parental) Observed 17% recombinant flies Suggested Incomplete linkage of genes

Crossing Over Prophase I: homologous chromosomes can “swap” alleles More variable gametes than simple mendelian rules would predict

Therefore, Crossing Over Explains:

Linkage Maps Ordered list of genetic loci along chromosome Based on recombination frequencies between two genes Higher % of recombination = farther apart More places in between genes for crossing over to occur and separate the genes

Linkage Maps The recombination frequency between cn and b is 9%. The recombination frequency between cn and vg is 9.5%. The recombination frequency between b and vg is 17%.

Linkage Maps Map units are the distances between genes on a chromosome. 1 map unit = 1% recombination 50% recombination = so far apart that crossing over is all but certain Remember, 50% recomb. = ind. assortment (non-homologous) Linkage maps show relative order/distance More recent studies show exact distances and order

Sex Chromosomes

X-Y Sex Determination X and Y behave as homologues Each egg receives an X from XX mother One sperm receives X and one Y Results in 50/50 chance of male or female SRY Gene Present (on Y) : gonads develop into testes (male) Not present (no Y): gonads become ovaries (female) SRY also regulates other genes

Sex-Linked Genes Sex chromosomes also contain other genes. (ie: drosophila eye color) Females must be homozygous recessive to display trait (XX – second X can mask recessive) Females can be carriers Males only need to inherit a single copy to show trait Can a male be a carrier?

Sex-Linked Disorders Duchenne Muscular Dystrophy 1/3500 males Progressive muscular weakening Die by mid-20’s Missing X-linked gene No production of dystrophin (muscle protein)

Sex-Linked Disorders Hemophilia Absence of one or more clotting factors affected individuals cannot stop bleeding normally treated with protein injections

Barr Bodies Only one of the females X chromosomes is active The other becomes a Barr body When assorted into an ovum, the Barr body becomes activated again Which X becomes Barr body is random in each cell Approx. 50% express each allele (if hetero)

X-Inactivation in Females

Nondisjunction Errors with meiotic spindle Meiosis I: Homologous tetrad doesn’t separate OR Meiosis II: Sister chromatids don’t separate Some gametes receive two of the same type of chromosome and another gamete receives no copy

Aneuploidy Results from fertilization involving nondisjoined gamete(s) Trisomy three copies of a particular chromosome (2n + 1) Monosomy only one copy of a particular chromosome (2n – 1)

Down Syndrome Three copies of chromosome 21 1/700 children born each year Definite link with maternal age

Aneuploidy in Sex Chromosomes XXY Male (Klinefelter’s Syndrome) Male sex organs, sterile w/ femininity XYY Males Tend to be taller than normal

Aneuploidy in Sex Chromosomes XXX Females Will develop as normal females XO Females (monosomy – Turner syndrome) Immature females 1/2500 live female births

Changes in Chromosomes