The locus for combined factor V-factor VIII deficiency (F5F8D) maps to 18q21, between D18S849 and D18S1103.
The locus for combined factor V-factor VIII deficiency (F5F8D) maps to 18q21, between D18S849 and D18S1103.
复制标题
V 因子-VIII 因子联合缺乏症 (F5F8D) 的基因座映射到 18q21，位于 D18S849 和 D18S1103 之间。
DOI：
10.1086/513897
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发表时间：
1997
影响因子：
9.8
通讯作者：
Tuddenham,EG
中科院分区：
文献类型：
--
作者：
Neerman-Arbez,M;Antonarakis,SE;Blouin,JL;Zeinali,S;Akhtari,M;Afshar,Y;Tuddenham,EG
合并因子V-因子VIII缺乏症（F5F8D）是一种罕见的常染色体隐性凝血疾病，其凝血因子V和凝血因子VIII的水平均降低。为了绘制并随后克隆导致该表型的基因，我们收集了来自19个家族（16个来自伊朗，2个来自巴基斯坦，1个来自阿尔及利亚）共32名受影响个体的DNA，利用信息丰富的DNA多态性基因型进行全基因组连锁搜索。除了两个家谱外，所有家谱都至少包含一个近亲婚姻。标记D18S1129在18q21的最大LOD评分（Zmax）为14.82,θ = 0.02；其他几个标记d18s849、D18S1103、D18S64和D18S862的LOD评分为bbbb9。多点分析得出D18S1129和D18S64区间的inZmax= 18.91。信息性重组将F5F8D基因座置于D18S849和D18S1103之间，间隔约1 cM。这些结果与最近报道的这种疾病与犹太家庭18q染色体的联系相似（Nichols et al. 1997），并提供证据表明同一基因负责人类群体中所有的F5F8D。无亲缘关系家族中该表型临床严重程度的差异，以及在伊朗近亲家族中未能检测到特定的DNA多态性单倍型，表明F5F8D基因存在不同的分子缺陷。在关键区域的两侧，存在明显无间隙连接的CEPH YACs。定位克隆F5F8D基因的工作正在进行中。
Combined factor V-factor VIII deficiency (F5F8D) is a rare, autosomal recessive coagulation disorder in which the levels of both coagulation factor V and coagulation factor VIII are diminished. In order to map and subsequently clone the gene responsible for this phenotype, DNAs from 19 families (16 from Iran, 2 from Pakistan, and 1 from Algeria) with a total of 32 affected individuals were collected for a genomewide linkage search using genotypes of highly informative DNA polymorphisms. All pedigrees except two contained at least one consanguineous marriage. A maximum LOD score (Zmax) of 14.82 for θ = .02 was generated with marker D18S1129 in 18q21; LOD scores > 9 were obtained for several other markers—D18S849, D18S1103, D18S64, and D18S862. Multipoint analysis resulted inZmax= 18.91 for the interval between D18S1129 and D18S64. Informative recombinants placed the locus for F5F8D between D18S849 and D18S1103, in an interval of ∼ 1 cM. These results are similar to the recently reported linkage of this disease to chromosome 18q in Jewish families (Nichols et al. 1997) and provide evidence that the same gene is responsible for all F5F8D among human populations. The difference in clinical severity of the phenotype in unrelated families, as well as the failure to detect a specific haplotype of DNA polymorphisms in the consanguineous Iranian families, suggests the existence of different molecular defects in the F5F8D gene. There exists an apparently gap-free contig with CEPH YACs linking the two markers on either side of the critical region. Positional cloning efforts are now in progress to clone the F5F8D gene.