State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Haemophilia. 2012 Jul;18(4):621-5. doi: 10.1111/j.1365-2516.2011.02732.x. Epub 2012 Jan 26.
Haemophilia A (HA) is the most common hereditary bleeding disorder caused by F8 gene mutation. Linkage analysis is an auxiliary strategy to direct mutation analysis for genetic counselling of HA. Here we characterize and validate a novel panel of six short tandem repeat (STR) loci for genetic counselling in Chinese HA pedigrees. The panel was analysed in 116 unrelated healthy female patients and 108 male patients, and verified in 169 unrelated pedigrees with HA. The six STR loci in the panel spanned a distance of 0.3 Mb from each side of the F8 gene. Three of them, F8Up226, F8Up146 and F8Down48, were first described here. Markers F8Up226, F8Up146, F8Int13, F8Int25, F8Down48 and DXS1073 exhibited the number of alleles 16, 9, 8, 6, 9 and 10, and heterozygosity rates of 74.8%, 44.8%, 60.9%, 42.6%, 61.7% and 62.0% respectively. Haplotype frequencies analysis suggested that the genotypes of haplotype provided a highly informative content (56.5%). The panel was informative in 167 of 169 unrelated haemophilic pedigrees with the combined diagnostic rate of 98.8%. In eight pedigrees could not be diagnosed by mutation detection linkage studies using the panel were informative in all the pedigrees and a reliable diagnosis was made in seven pedigrees. The novel panel of the six STR loci represents a high degree of informativeness and a low fraction of recombination. Linkage analysis using this panel provides an alternative strategy when direct mutation detection is not feasible for genetic counselling in Chinese HA families.
甲型血友病（HA）是最常见的遗传性出血性疾病，由 F8 基因突变引起。连锁分析是 HA 遗传咨询中指导基因突变分析的辅助策略。在这里，我们对一组新的六个短串联重复（STR）位点进行了特征描述和验证，用于中国 HA 家系的遗传咨询。该panel 在 116 名无关健康女性患者和 108 名男性患者中进行了分析，并在 169 个无关的 HA 家系中进行了验证。panel 中的六个 STR 位点位于 F8 基因两侧 0.3 Mb 处。其中三个位点，F8Up226、F8Up146 和 F8Down48，是首次在此描述。标记物 F8Up226、F8Up146、F8Int13、F8Int25、F8Down48 和 DXS1073 表现出 16、9、8、6、9 和 10 个等位基因，杂合率分别为 74.8%、44.8%、60.9%、42.6%、61.7%和 62.0%。单体型频率分析表明，单体型基因型提供了高度信息含量（56.5%）。该 panel 在 169 个无关的血友病家系中，167 个家系具有信息性，综合诊断率为 98.8%。在 8 个不能通过panel 进行突变检测连锁研究进行诊断的家系中，所有家系都具有信息性，在 7 个家系中做出了可靠的诊断。该panel 中的六个 STR 位点代表了高度的信息量和低的重组率。当直接突变检测不适用于中国 HA 家族的遗传咨询时，该panel 的连锁分析提供了一种替代策略。
