Haley C S
AFRC Institute of Animal Physiology and Genetics Research, Edinburgh Research Station, Roslin, Midlothian, UK.
Anim Genet. 1991;22(3):259-77. doi: 10.1111/j.1365-2052.1991.tb00676.x.
The detection of marker loci linked to major genes or quantitative trait loci (QTL) of large effect in farm animal populations is of great potential value, both because it allows the easy manipulation of the major genes and because it provides a possible route to their ultimate isolation. At present the number of markers available is limited in farm animals. DNA fingerprints provide a promising source of informative marker loci and have the advantage that several loci can be detected on a single Southern hybridization. The disadvantage of DNA fingerprints is the difficulty in determining allelism of DNA fingerprint bands in different pedigrees and the fact that not all potentially resolvable loci can be resolved in a single pedigree. With probes capable of detecting 50 randomly distributed loci, about 50% of the genome of a typical domestic mammal might be expected to be closely linked to a marker (at a distance of 0.2 Morgans or less). If a proportion of DNA fingerprint loci prove to be clustered near chromosomal telomeres or elsewhere in the genome, coverage will be less. In order to detect linkage to a major gene, sires known or suspected to be heterozygous are used to produce large half-sibships, all animals in the pedigree are DNA fingerprinted and the phenotypes of the offspring are recorded. Where several heterozygous sires are available, sires can be selected in an attempt to maximize the number of marker loci resolved. The optimum number of sires needed to produce pedigrees will depend upon the size of the major gene, the number of DNA fingerprint probes available and the characteristics of the DNA fingerprints produced, but often one or two pedigrees will be optimum. Monte Carlo simulation was used to explore the power of detection of linkage between a major gene and a marker locus in a backcross. Maximum likelihood and analysis of variance of mean differences between marker genotypes were of similar power, but maximum likelihood provided reasonable estimates of the major gene effect and its linkage to the marker under some circumstances. One hundred offspring informative for the segregation of a marker would provide reasonable power for the detection of a gene causing a difference between the heterozygote and the homozygote of at least one within-sire, within-genotype standard deviation when linkage was very close (0.05 or less).(ABSTRACT TRUNCATED AT 400 WORDS)
在农场动物群体中，检测与主要基因或具有较大效应的数量性状基因座（QTL）连锁的标记基因座具有巨大的潜在价值，这既是因为它能使主要基因易于操作，也是因为它为最终分离这些基因提供了一条可能的途径。目前，农场动物中可用的标记数量有限。DNA指纹图谱提供了一种很有前景的信息丰富的标记基因座来源，其优点是在一次Southern杂交中可以检测到多个基因座。DNA指纹图谱的缺点是难以确定不同家系中DNA指纹条带的等位性，以及并非所有潜在可分辨的基因座都能在单个家系中得到分辨。使用能够检测50个随机分布基因座的探针，预计典型家养哺乳动物基因组的约50%可能与一个标记紧密连锁（距离为0.2摩根或更小）。如果一部分DNA指纹基因座被证明聚集在染色体端粒附近或基因组的其他地方，覆盖范围将会更小。为了检测与主要基因的连锁，已知或怀疑为杂合子的父本被用来产生大型半同胞家系，家系中的所有动物都进行DNA指纹图谱分析，并记录后代的表型。如果有几个杂合子父本可用，可以选择父本以尽量增加分辨出的标记基因座数量。产生家系所需的最佳父本数量将取决于主要基因的大小、可用的DNA指纹探针数量以及所产生的DNA指纹图谱的特征，但通常一两个家系是最佳的。采用蒙特卡罗模拟来探究回交中主要基因与标记基因座之间连锁的检测能力。标记基因型之间平均差异的最大似然法和方差分析具有相似的能力，但在某些情况下，最大似然法能提供主要基因效应及其与标记连锁的合理估计。当连锁非常紧密（0.05或更小）时，100个对标记分离有信息的后代将为检测导致杂合子和纯合子之间差异至少为一个父本内、基因型内标准差的基因提供合理的能力。
