Gene Mapping and Crossing Over – Genetics Gene Mapping and Crossing Over – Ch5-p.115 Gene Linkage & Genetic Mapping

Gene Mapping determines order of genes & relative distances between them 1 map unit = 1 cM (centimorgan) 1 locus; 2 loci B b A A a b a B A & B are Cis arrangement (coupled) Trans arrangement (repulsed)

Gene Distance recombination frequencies between alleles: determine relative distance between them proportional to their distance apart 1% recombination = 1 map unit = 1 cM B F A A a b a f 10% recombination 45% recombination

% Recombination <50% recombination --> genes linked on same chromosome >50% recombination --> genes are far apart on chromosome acts like genes are unlinked (indep. assort.)

Chi-Square (X2)Analysis: “Goodness of Fit” +a+b : +abb : aa+b : aabb normal bent albino albino/bent 1/4 : 1/4 : 1/4 : 1/4 expected proportion observed # 21 26 27 26 = 100 total expected # 1/4x100 1/4x100 1/4x100 1/4x100 25 25 25 25 X2 = (21-25)2 + (26-25)2 + (27-25)2 + (26-25)2 25 25 25 25 0.89 = 16 + 1 + 4 + 1 = 22 25 25 25 25 25

Chi-Square Interpretation X2 = 0.89 d.f. (degree of freedom) = # phenotypes - 1 d.f. = 4 - 1 = 3 probability .05 (95% confidence level) of being different from expected w/ d.f. 3 = 7.82 (read off a chart) if X2 < p.05, then observed and expected are not statistically different Therefore, 2 traits are not linked on same chromosomes and independent assortment occurs 0.89 < 7.82, therefore not linked

How does linkage affect Mendelian segregation patterns? Discovery of genetic linkage in Drosophila (Thomas H. Morgan, ~1911) Morgan determined that the gene for white-eyes (w) and a gene for miniature wings (m) occur on the X-chromosome. Cross female white-miniature (wm/wm) & wild type male (w+m+/Y): wm x w+m+  w+m+ & wm wm (Y) wm (Y) F1  wild type (w+m+/wm) females and white-eyed miniature wing (wm/ Y) males.

Discovery of genetic linkage in Drosophila (Thomas H. Morgan, ~1911) F1 x F1  w+m+ x wm wm (Y) F2 “parental” genotypes and phenotypes (same allele states as F1): w+m+ wild-type female (n = 439) wm w+m+ wild-type male (n = 352) (Y) wm white-eye/miniature female (n = 359) wm white-eye/miniature male (n = 391)

Morgan also observed F2 non-parental genotypes and phenotypes: w+m wild-type eye/miniature female (n = 235) wm w+m wild-type eye/miniature male (n = 210) (Y) wm + white-eye/wild-type wing female (n = 218) wm+ white-eye/wild-type wing male (n = 237) F1 x F1  w+m x wm wm+ (Y) Non-parental combinations of linked genes are called recombinants. 50% recombinant phenotypes are expected if independent assortment occurs. Morgan observed 900/2,441 (36.9%) recombinant phenotypes and concluded that the two genes must be linked.

Fig. 13.1, Morgan’s experimental cross of white-eyes and miniature wings.

Morgan also observed and hypothesized: Parental phenotypes always were more common in many other types of crosses, and recombinant phenotypes occurred less frequently. During meiosis, some alleles assort together because they lie adjacent to each other on the same chromosome. The closer two genes are on the chromosome, the more likely they are to remain together during meiosis. Recombinants are produced by crossing-over.

Fig. 13.2, Mechanism of crossing-over gives rise to recombinant (non-parental) genotypes and phenotypes for linked genes.

Some basics terminology about crossing-over: Crossing over occurs in prophase I of meiosis I. Chiasma (pl. chiasmata) is the site where crossing-over occurs. Crossing-over is a reciprocal exchange of DNA, involving breaking and rejoining of homologous chromatids. Crossing-over leads to recombination between linked genes and produces novel genetic variation.

When does crossing over occur? Possibilities: Prophase I of meiosis I: 4-chromatid stage after chromosomes are duplicated Interphase prior to meiosis: 2-chromatid stage before chromosomes are duplicated Ordered tetrad experiments with Neurospora crassa (orange bread mold) and the arrangement of ascospores in the ascus indicate the pattern of crossing over. Experiments indicate that crossing over occurs at the 4-chromatid stage (prophase I of meiosis).

Constructing genetic maps: Number (%) of genetic recombinants produced reflects gene linkage relationships. Recombination experiments can be used to generate genetic maps.

Concept of a genetic map (cont.): Cross-over is more likely to occur between distant genes than close genes (see Fig. 13.6).

First genetic map was for Drosophila: 3 sex-linked genes w = white-eyes m =miniature wings y = yellow body Recombination frequencies: w x m = 32.6 w x y = 1.3 m x y = 33.9 y w m 1.3 mu 32.6 mu

Mitotic recombination: Crossing-over sometimes occurs in mitosis (i.e., somatic cells)! First observed by Curt Stern (1936) in heterozygous Drosophila carrying sex-linked mutations for yellow body color (y+/y) and singed bristles (sn/sn+). Mitotic cross-over occurred in heterozygotes and appeared as a mosaic of two different phenotypes in the same individual. Possibly explained by non-disjunction, but mosaic regions were always adjacent,and therefore likely to be products of the same genetic event. Fig. 13.22

Fig. 13.24, Mitotic cross-over in Drosophila