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Review
. 2003 Jul;73(1):5-16.
doi: 10.1086/376419. Epub 2003 May 22.

Hot and cold spots of recombination in the human genome: the reason we should find them and how this can be achieved

Norman Arnheim  1 , Peter Calabrese, Magnus Nordborg
Affiliations
Review

Hot and cold spots of recombination in the human genome: the reason we should find them and how this can be achieved

Norman Arnheim et al. Am J Hum Genet. 2003 Jul.
No abstract available

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Figures

Figure 1
Figure 1
Basic principle of single-sperm typing. A, The sperm donor is heterozygous at both the A/a and I/i loci. The four possible sperm haplotypes with respect to these two loci are shown (NR = nonrecombinant; R = recombinant). B, Sperm lysis followed by simultaneous PCR, using primers specific for the A/a and I/i loci. Separate aliquots of the PCR product can be typed for the A/a or I/i markers, thereby determining the haplotype that, in this case, is Ai.
Figure 2
Figure 2
Basic principle of PEP. To make multiple copies of a single-sperm genome, individual sperm are lysed, and a collection of all possible 15-nt-long primers is annealed to the DNA and extended multiple times (usually 50–60) by use of Taq DNA polymerase. The dashed lines show the primer extension products after several rounds and indicate that multiple copies of each genomic sequence can be produced. Aliquots of the product are placed in tubes (inverted triangles) and used for genotyping.
Figure 3
Figure 3
Single-sperm bisection strategy. The genotype of the sperm donor at nine loci (A/a through I/i) is shown at the top. After PEP, sperm are identified that have a crossover between the A/a and I/i loci. Successive PEP aliquots are taken for additional typings and, at each step, the marker in the middle of the smallest interval (*) in which the crossover could have occurred is examined until the desired resolution is achieved.
Figure 4
Figure 4
Principle of identification of crossover molecules by use of allele-specific PCR. The four possible products of meiosis, including both nonrecombinants (NR1 and NR2) and recombinants (R1 and R2), are shown. For each meiotic product, both strands of the double-stranded DNA molecule are shown. The interval being studied is bounded on each side by an SNP (two are required on each side, but, for simplicity, only one is shown; see text). For each SNP, one allele contains an A/T base pair and the other allele a G/C base pair. The four haplotypes, with respect to these two SNPs, are also shown. To select for the R1 haplotype (A/T on the left and G/C on the right), PCR primers specific for A/T and G/C sites are used for PCR. The primer on the left of the interval contains a T at the 3′ end, whereas the primer on the right contains a G at its 3′ end. At each SNP, the primer is extended efficiently (thick arrows) on two of the four haplotypes but inefficiently (thin arrows with an X) on the remaining two haplotypes, because of a T opposite G base-pair mismatch. As a result, only R1 molecules can be efficiently amplified with the two primers.
See this image and copyright information in PMC

References

Electronic-Database Information

    1. HapMap, http://www.genome.gov/page.cfm?pageID=10001688

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