Rest of Chapter 5 Human recombination studies Mapping

Rest of Chapter 5 • Human recombination studies • Mapping by tetrad analysis in fungi • Analysis of ordered tetrads • Other features of recombination.

Human pedigrees and mapping • In humans, progeny numbers are small. • Matings cannot be arranged for experiments. • Coupling (AB/ab) vs. repulsion (Ab/a. B) heterozygotes cannot be distinguished most of the time. • Pedigrees can be pooled.

Lod scores

Fungi in genetic studies • Haploid organisms can have genetic maps made by using spore analysis. • No testcrosses are needed. • (review of fungal biology)

The life cycle of the baker’s yeast (Saccharomyces cerevisiae)

Types of tetrads PD = parental ditype NPD = Nonparental ditype (no linkage, PD=NPD) (with linkage, PD>NPD) TT = Tetratype tetrad

Tetrad analysis of unlinked genes using unordered asci For unlinked genes, parental ditype (PD) (having 2 kinds of spores) and nonparental ditype (NPD) asci are produced in equal proportion For unlinked genes, recombination between one of the genes and its centromere produces tetratype asci (TT) having 4 kinds of spores

Tetrad analysis results for linked genes in unordered tetrads-1 No crossovers or 2 -strand double crossovers result in parental ditype (PD) asci. One recombination between the genes results in tetratype (TT) asci

Tetrad analysis results for linked genes in unordered tetrads-2 Three-strand double crossovers give the same result as a single crossover, tetratype asci (TT). Fourstrand double crossovers give non-parental ditype (NPD) asci. As a result, for linked genes, PD >> NPD.

Mapping with unordered tetrads: • Map distance=(½)[TT]2[NPD]+4[NPD]/total • ={(½)[TT]+3[NPD]/total # of tetrads }x 100

A branch diagram for analyzing unordered tetrads data

The life cycle of an ascomycete fungus with ordered tetrads

Analysis of ordered tetrad data Ordered tetrads allow one to map the distance between a gene and its centromere. No crossover between a gene and its centromere gives first division segregation. A crossover between a gene and its centromere gives a second division segregation.

Other types of recombination studies • Recombination within genes • Mitotic recombination

Fine structure mapping allows mapping the internal structure of a locus. Cistron – defines one genetic function = mutations that fail to complement The term comes from cis and trans. Lozenge gene in Drosophila:

X + lz. BS+ + + +lzg v X X ______ x ________> Y ct +lzg ct-lz=7. 7 c. M lz-v=5. 3 c. M 134 out of 16, 000 progeny had normal eyes Frequency of recombination=0. 008 What happened? X ct ++ + in all nonlozenge females and X + lz. BSlzg v in 5 males with ‘new’ lz phenotype.

Somatic recombination (mitotic crossover) can lead to twin spots