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Genetics 301 Lecture #7
Spring 2003, February 4, 2003

Map distances on chromosomes are calculated by adding the map distances for the smallest intervals between the two genes of interest. Map distances for genes on the same chromosome may be quite large, reflecting multiple crossovers between the pair of homologs. The recombinant fraction between any two genes on the same chromosome, however, will not normally exceed 50%. This reflects the fact that multiple crossovers tend to average out to 50% recombinant progeny.

The three point cross allows detailed analysis of recombination in a region of a chromosome. (Worked through text example Problem 2 at end of Chapter 4). The recombinant frequency in each region will be the sum of the two single crossover types plus the two double crossover types. Map distance will be this value expressed as a percentage of the total progeny. The largest recombinant proportion will be for the two genes that are furthest apart from each other on the chromosome. The coefficient of coincidence ( c ) equals observed double crossover types / expected double crossover types. Expected double crossover types equals (recombinant fraction in region I) X (recombinant fraction in region II) X (total progeny). C will usually be less than one. Interference (I) equals 1 – c. The higher the interference value, the greater the degree that a second crossover is suppressed. Heterochromatin also suppresses crossing over. The physical distance in heterochromatin regions is relatively greater than the genetic distance.

Polymorphisms (common genetic variations within a species) allow the construction of genetic maps in species such as humans which lack large numbers of mutants or the ability to conduct controlled crosses. Protein polymorphisms detectable by protein electrophoresis were detectable by the 1960s, but did not provide enough markers (<100) to construct detailed maps.

Three types of DNA polymorphisms have allowed detailed genetic maps to be developed for humans. (1) Restriction fragment length polymorphisms (RFLPs) detect variations in the size of bands detected by DNA electrophoresis, often resulting from mutations resulting in loss or gain of a restriction enzyme cleavage site. (2) Simple tandem repeat polymorphisms (STRPs) are variations resulting from varying numbers of repeat units for a simple repeat such as (TG) repeated many times. RFLPs may sometimes reflect this type of variation rather than cut site changes. These polymorphisms are also detectable in several ways to be described later. (3) Single nucleotide polymorphisms (SNPs) reflect single base substitutions in the DNA sequence. On the average such changes seem to be present about every 1,000 bases. Techniques are rapidly developing which should allow large scale screening for such polymorphisms.

Relating DNA to the genetic map, it appears that there is about 1% recombination (1 cM) per 1 million bases (1 Mb) of DNA in humans. Chromosome 1, the largest chromosome, has about 250 Mb and thus is expected to have about 250 cM map distance, or an average of 5 crossover events.

Tetrad analysis is possible in some fungi (e.g., yeast, Neurospora) and involves genetic typing of all of the products of a single meiosis. In yeast this involves the analysis of four unordered ascospores found within a sac (ascus). In Neurospora this involves analysis of 8 ordered ascopsores found in an ascus in the same order as the chromosomes in meiosis.

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