Confirmation of linkage of type 1 hereditary sensory neuropathy to human chromosome 9q22
Confirmation of linkage of type 1 hereditary sensory neuropathy to human chromosome 9q22
复制标题
证实 1 型遗传性感觉神经病与人类染色体 9q22 连锁
作者：
K. Bejaoui;D. McKenna;B. Hosler;E. Burns;L.M. Deater;G. O'neill;J. Haines;R. Brown
目的：1）在一个德国血统的美国大家族中证实遗传性感觉神经病1型（HSN-1）与人类染色体9 q22的连锁。2)构建跨越HSN-1候选区间的酵母人工染色体（YAC）重叠群。3)研究HSN-I重叠群中潜在的候选基因。背景资料：HSN-I是一种罕见的周围神经病，其特征是失去温度感，溃疡和骨髓炎的手指，和微妙的远端无力。HSN-I基因先前已在4个澳大利亚家族中定位于人类染色体9q22.1-q22.3，在标记D9 S318和D9 S176之间，间隔为8 cM。研究方法：在一个大的德国-美国家庭与HSN-I，全基因组连锁分析进行了68个家庭成员超过五代，包括17个受影响的成员。采用PCR进行基因分型，并使用Fastlink进行两点连锁分析。基于Whitehead Institute YAC重叠群WC9.3构建YAC重叠群。结果：两点连锁分析结果表明，D9 S1815在θ = 0时的最大lod值为8.2。单倍型分析将HSN-I基因定位在标记D9 S1797和D9 S197之间。使用来自Centre d 'Etude du Polymorphism Humain YAC Library的YAC克隆，我们构建了跨越这些标记的YAC重叠群。根据人类基因组的辐射杂交图谱，我们估计这个区间的大小小于2,500 kb。结论：我们的研究证实了一个假定的HSN-I基因与染色体9 q22的连锁，大大缩小了HSN-I位点，并为HSN-I基因的鉴定提供了基础。
Objectives: 1) To confirm linkage of hereditary sensory neuropathy type 1 (HSN-I) to human chromosome 9q22 in a large American family of German origin. 2) To construct a yeast artificial chromosome (YAC) contig spanning the HSN-I candidate interval. 3) To investigate the HSN-I contig for potential candidate genes. Background: HSN-I is a rare peripheral neuropathy characterized by loss of temperature sensation, ulceration and osteomyelitis of the digits, and subtle distal weakness. A gene for HSN-I has previously been mapped to human chromosome 9q22.1-q22.3 between markers D9S318 and D9S176 in an 8-cM interval in four Australian families. Methods: In a large German-American family with HSN-I, genome-wide linkage analysis was performed on 68 family members extending over five generations and including 17 affected members. Genotyping was performed with PCR, and the resulting genotypes were analyzed with two-point linkage analysis with Fastlink. A YAC contig was constructed based on the Whitehead Institute YAC contig WC9.3. Results: Two-point linkage analysis resulted in a maximum lod score of 8.2 at θ = 0 for marker D9S1815. Haplotype analysis locates the HSN-I gene between markers D9S1797 and D9S197. Using YAC clones from the Centre d’Etude du Polymorphism Humain YAC Library, we constructed a YAC contig spanning these markers. Based on the radiation hybrid map of the human genome, we estimate that the size of this interval is less than 2,500 kb. Conclusions: Our study confirms linkage of a putative HSN-I gene to chromosome 9q22, considerably narrows the HSN-I locus, and provides a basis for identification of the HSN-I gene.
影响因子：
4.4
作者：
NAKAGAWARA, A;LIU, XC;BRODEUR, GM
通讯作者：
BRODEUR, GM
影响因子：
4.4
作者：
ELMAGHRABI, MR;LANGE, AJ;PILKIS, SJ
通讯作者：
PILKIS, SJ
评估拟议的复杂遗传性状连锁研究的功效。
影响因子：
9.8
作者：
Ploughman,LM;Boehnke,M
通讯作者：
Boehnke,M