POSITIONAL CLONING OF THE NUDE LOCUS - GENETIC, PHYSICAL, AND TRANSCRIPTION MAPS OF THE REGION AND MUTATIONS IN THE MOUSE AND RAT
POSITIONAL CLONING OF THE NUDE LOCUS - GENETIC, PHYSICAL, AND TRANSCRIPTION MAPS OF THE REGION AND MUTATIONS IN THE MOUSE AND RAT
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DOI：
10.1006/geno.1995.1187
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发表时间：
1995-08-10
期刊：
影响因子：
4.4
通讯作者：
LANDER, ES
中科院分区：
文献类型：
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作者：
SEGRE, JA;NEMHAUSER, JL;LANDER, ES
在小鼠和大鼠中，裸体基因的突变会产生多效性的无毛和动症表型，导致免疫系统严重受损。为了鉴定致病基因，我们利用了现代的定位克隆工具和技术。具体地说，我们构建了一个多态标记的遗传图谱，酵母人工染色体和噬菌体P1克隆的物理图谱，以及通过直接选择和外显子捕获获得的基因转录图谱。我们鉴定了7个与果蝇、秀丽线虫、大鼠或人的基因相似的新转录本，以及3个先前鉴定的小鼠基因。基于我们的转录定位结果，我们提出了一种新的方法来估计一个区域中的基因数量，并估计裸露基因座位于大约三倍于基因丰富的区域。我们证实了最近发表的一篇报道，即裸露表型是由编码新的有翼螺旋或叉头域转录因子Whn的基因突变引起的(Nehls等人，自然372：103-107,1994)。我们还报告了大鼠RNU等位基因的突变和大鼠WHN mRNA的完整编码序列。(C)1995年学术出版社。
Mutations in the nude locus in mice and rats produce the pleiotropic phenotype of hairlessness and athymia, resulting in severely compromised immune system. To identify the causative gene, we utilized modern tools and techniques of positional cloning. Specifically, spanning the region in which the nude locus resides, we constructed a genetic map of polymorphic markers, a physical map of yeast artificial chromosomes and bacteriophage P1 clones, and a transcription map of genes obtained by direct cDNA selection and exon trapping. We identified seven novel transcripts with similarity to genes from Drosophila, Caenorhabditis elegans, rat, or human and three previously identified mouse genes. Based on our transcription mapping results, we present a novel approach to estimate the number of genes in a region and estimate that the nude locus resides in a region approximately threefold enriched for genes. We confirm a recently published report that the nude phenotype is caused by mutations in a gene encoding a novel winged helix or fork head domain transcription factor, whn (Nehls et al., Nature 372: 103-107, 1994). We report as well the mutations in the rat rnu allele and the complete coding sequence of the rat whn mRNA. (C) 1995 Academic Press, Inc.