Valle Y, Padilla-Gutiérrez J R, Quintero-Ramos A, García-González I J, Rivas F
Departamento de Clínicas Médicas, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Mexico.
Genet Mol Res. 2013 Aug 8;12(3):2821-8. doi: 10.4238/2013.August.8.2.
Recombination patterns can be indirectly inferred by means of linkage disequilibrium (LD) estimates, since LD is negatively correlated with genetic distance. However, LD does not necessarily have absolute correspondence with genetic distance. We estimated LD at 5 loci located in the 21q22.3 region. These STRs (D21S1440, D21S168, D21S1260, D21S1446, and D21S1411) covered 8.81 Mb of the 21q22.3 region. They were genotyped by conventional PCR. Similar size samples previously validated by sequencing were used as a genotyping control. Three hundred and sixty-nine individuals (62 families) living in Guadalajara, Mexico, were included. As an inclusion criterion, each family had a positive paternity test by autosomal markers for the CODIS core loci. Two hundred and thirty phase known haplotypes were identified by familial segregation. Only those haplotypes whose frequency was higher than 4% were taken into account for LD estimation, expressed as Lewontin's D' coefficient and Bonferroni's correction P values. For all 5 loci, the genetic distributions were in agreement with Hardy-Weinberg expectations. Heterozygosity and haplotype diversity were ≥ 0.69 and 99.58%, respectively. D21S1440-D21S168 (4.51 cM) and D21S1446-D21S1411 (4.58 cM) marker haplotype frequencies were significantly different from those expected by random distribution. The remaining haplotypes, including those with minimal inter-distance (D21S1260-D21S1446, 1.44 Mb), did not show LD. The 5 STRs at the 21q22.3 region in this Mexican population showed a non-homogeneous LD pattern, which demonstrates that recombination or linkage should not be assumed solely on the basis of genetic distance.
由于连锁不平衡（LD）与遗传距离呈负相关，因此可以通过LD估计间接推断重组模式。然而，LD与遗传距离不一定具有绝对的对应关系。我们估计了位于21q22.3区域的5个位点的LD。这些短串联重复序列（STRs，即D21S1440、D21S168、D21S1260、D21S1446和D21S1411）覆盖了21q22.3区域的8.81兆碱基对。通过常规聚合酶链反应（PCR）对它们进行基因分型。先前通过测序验证的大小相似的样本用作基因分型对照。纳入了居住在墨西哥瓜达拉哈拉的369个人（62个家庭）。作为纳入标准，每个家庭通过常染色体标记对联合DNA索引系统（CODIS）核心位点进行的亲子鉴定呈阳性。通过家族分离鉴定出230个已知相位的单倍型。在进行LD估计时，仅考虑那些频率高于4%的单倍型，以Lewontin's D'系数和Bonferroni校正P值表示。对于所有5个位点，遗传分布均符合哈迪-温伯格预期。杂合度和单倍型多样性分别≥0.69和99.58%。D21S1440-D21S168（4.51厘摩）和D21S1446-D21S1411（4.58厘摩）标记单倍型频率与随机分布预期的频率显著不同。其余单倍型，包括那些间距最小的单倍型（D21S1260-D21S1446，1.44兆碱基对），未显示出LD。该墨西哥人群21q22.3区域的5个STR显示出不均匀的LD模式，这表明不应仅基于遗传距离来假定重组或连锁关系。
