Péterfy M, Phan J, Oswell G M, Xu P, Reue K
Department of Medicine, University of California at Los Angeles, Los Angeles, California 90095, USA.
Genomics. 1999 Dec 15;62(3):436-44. doi: 10.1006/geno.1999.6023.
The fatty liver dystrophy (fld) mutation is manifested in abnormalities of lipid and glucose metabolism and peripheral neuropathy. To identify the gene affected by this mutation, we generated a genetic map of the fld region on chromosome 12 by the analysis of F2 offspring from an intersubspecific cross between strains BALB/cByJ-fld and CAST/EiJ. The results localize fld to the 0.42-cM interval between the microsatellite markers D12Mit170 and D12Mit184. A contig of YACs and BACs covering the nonrecombinant genomic region has been constructed and used for the identification of genes. Expressed sequence tag mapping and exon trapping identified three transcripts within the critical interval: Ctla2b, which encodes a cysteine protease inhibitor, and mouse homologs of KIAA0188 and KIAA0575, two long human transcripts of unknown function. Expression analysis revealed that Kiaa0188 is expressed in wildtype but not in fld liver, implicating this gene as a candidate for harboring the fld mutation.
脂肪肝营养不良（fld）突变表现为脂质和葡萄糖代谢异常以及周围神经病变。为了鉴定受此突变影响的基因，我们通过分析BALB/cByJ-fld和CAST/EiJ品系间亚种间杂交的F2后代，构建了12号染色体上fld区域的遗传图谱。结果将fld定位在微卫星标记D12Mit170和D12Mit184之间0.42厘摩的区间内。已经构建了覆盖非重组基因组区域的酵母人工染色体（YAC）和细菌人工染色体（BAC）重叠群，并用于基因鉴定。表达序列标签定位和外显子捕获在关键区间内鉴定出三个转录本：Ctla2b，其编码一种半胱氨酸蛋白酶抑制剂，以及KIAA0188和KIAA0575的小鼠同源物，这是两个功能未知的人类长转录本。表达分析显示，Kiaa0188在野生型肝脏中表达，但在fld肝脏中不表达，这表明该基因是携带fld突变的候选基因。
