Loc

CNN2 NDUFS7 MKNK2 ATCAY ZBTB7A L C19orf10 PLAC2 ZNF136 OR10H1 COPE CILP2 MGC4093 LOC653583 DHX34 LIN7B TIP39 DPRX CNOT3 RPS9 NALP8

Figure 2.17 Maps for human chromosomes 18 (left) and 19 (right) showing chromosome regions, the physical locations of identified genes and open reading frames (labeled orf ) along the chromosomes, and the names and locations of a subset of genes. Chromosome 18 is about 85 million bp and chromosome 19 is about 67 million bp. Maps from NCBI Map Viewer based on data as of January 2008.

meiosis and exchange short segments, a process known as crossing-over (Fig. 2.18).

Linkage of loci has the potential to impact multi-locus genotype frequencies and violate Mendel's law of independent segregation, which assumes the absence of linkage. To generalize expectations for genotype frequencies for two (or more) loci requires a model that accounts explicitly for linkage by including the rate of recombination between loci. The effects of linkage and recombination are important determinants of whether or not expected genotype frequencies under independent segregation of two loci (Mendel's second law) are met. Autosomal linkage is the general case that will be used to develop expectations for genotype frequencies under linkage.

The frequency of a two-locus gamete haplotype will depend on two factors: (i) allele frequencies and (ii) the amount of recombination between the two loci. We can begin to construct a model based on the recombination rate by asking what gametes are generated by the genotype A1A2B1B2. Throughout this section loci are indicated by the letters, alleles at the loci by the numerical subscripts and allele frequencies indicated by p1 and p2 for locus A and q1 and q2 for locus B. The problem is easier to conceptualize if we draw the two locus genotype as being on two lines akin to chromosomal strands

A_Bi a2 B2

Given this physical arrangement of the two loci, what are the gametes produced during meiosis with and without recombination events?

A1B1 and A2B2 "Coupling" gametes: alleles on the same chromosome remain together (term coined by Bateson and Punnett).

A1B2 and A2B1 "Repulsion" gametes: alleles on the same chromosome seem repulsed by each other and pair with alleles on the opposite strand (term coined by Thomas Hunt Morgan).

The recombination fraction, symbolized as r (or sometimes c), refers to the total frequency of gametes resulting from recombination events between two loci. Using r to express an arbitrary recombination fraction, let's build an expectation for the frequency of coupling and repulsion gametes. If r is the rate of recombination, then 1 - r is the rate of non-recombination since the frequency of all gametes is one, or 100%. Within each of these two categories of gametes (coupling and repulsion), two types of gametes are produced so the frequency of each gamete type is half that of the total frequency for the gamete category. We can also determine the expected frequencies of each gamete under random association of the alleles at the two loci based on Mendel's law of independent segregation.

Figure 2.18 A schematic diagram of the process of recombination between two loci, A and B. Two double-stranded chromosomes (drawn in different colors) exchange strands and form a Holliday structure. The crossover event can resolve into either of two recombinant chromosomes that generate new combinations of alleles at the two loci. The chance of a crossover event occurring generally increases as the distance between loci increases. Two loci are independent when the probability of recombination and non-recombination are both equal to V2. Gene conversion, a double crossover event without exchange of flanking strands, is not shown.

Gamete

Frequency

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