Further refinement of the Usher 2A locus at 1q41
Further refinement of the Usher 2A locus at 1q41
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DOI：
10.1136/jmg.35.9.773
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发表时间：
1998-09-01
影响因子：
4
通讯作者：
Bhattacharya, SS
中科院分区：
文献类型：
--
作者：
Bessant, DAR;Payne, AM;Bhattacharya, SS
USH综合征(USH)以先天性感音神经性耳聋和进行性色素视网膜病变为特征。三个亚型(USH1、USH2和USH3)均为隐性遗传。Usher 2型(USH2)患者具有正常的前庭反应和中到重度的听力损失。这些综合征被发现具有遗传异质性，USH2在1q41(USH2A)有一个基因座，USH1有6个基因座，USH3有1个基因座。一些USH2家族被排除在1q41基因座之外，这表明一定存在第二个尚未鉴定的基因座(USH2B)。连锁研究表明，大约90%的USH2家系是USH2A。对4个USH2家系进行了与USH2A基因侧翼标记的连锁分析。在这些家系中的一个中，在受影响的受试者中观察到了重组事件，该重组事件排除了标记AFM143XF10近端的USH2A基因，并将其定义为USH2A基因座的新的着丝粒侧翼标记。该家系中另一个患者的进一步重组事件证实AFM144XF2是端粒侧翼标记，这些多态标记之间的间隔估计为400kb。该区域完全包含在CEPH文库中的三个YAC中：867g9、919h3和848b9。这种改进将关键的遗传间隔缩短了一半以上，并将极大地促进USH2A基因的定位克隆。
Usher syndrome (USH) is characterised by congenital sensorineural hearing loss and progressive pigmentary retinopathy. All three subtypes (USH1, USH2, and USH3) are inherited as recessive traits. People with Usher type 2 (USH2) have normal vestibular responses and moderate to severe hearing loss.These syndromes have been found to be genetically heterogeneous, with a single locus for USH2 at 1q41 (USH2A), six loci for USH1, and one for USH3. Some USH2 families have been excluded fi om the 1q41 locus suggesting that a second, as yet unidentified, locus (USH2B) must exist. Linkage studies suggest that around 90% of USH2 families are USH2A.Four USH2 families were analysed for linkage to markers flanking the USH2A locus. In one of these families a recombination event was observed in an affected subject which excludes the USH2A gene from proximal to the marker AFM143XF10 and defines this as the new centromeric flanking marker for the USH2A locus. A further recombination event in another patient from this family confirmed AFM144XF2 as the telomeric flanking marker.The interval between these polymorphic markers is estimated to be 400 kb. This region is completely contained in each of three YACs from the CEPH library: 867g9, 919h3, and 848b9. This refinement more than halves the critical genetic interval and will greatly facilitate positional cloning of the USH2A gene.