Maas R L, Jepeal L I, Elfering S L, Holcombe R F, Morton C C, Eddy R L, Byers M G, Shows T B, Leder P
Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115.
Am J Hum Genet. 1991 Apr;48(4):687-95.
The murine limb deformity (ld) locus resides on mouse chromosome 2 and gives rise to a recessively inherited, characteristic limb deformity/renal aplasia phenotype. In this locus in the mouse, a gene, termed the "formin" gene, has been identified which encodes an array of differentially processed transcripts in both adult and embryonic tissues. A set of these transcripts are disrupted in independent mutant mouse ld alleles. We wish to report the isolation of a human genomic clone which is homologous to the mouse formin gene by virtue of sequence comparison and expression of conserved exons. Among human fetal tissues analyzed, the kidney appears to be a major site of expression. This human gene, LD, maps to chromosome 15q11----qter in mouse human somatic cell hybrids and, specifically, to 15q13----q14 by chromosomal in situ hybridization. This localization establishes both LD and beta 2-microglobulin as syntenic genes on mouse chromosome 2 and human chromosome 15 and implies the interspecies conservation of the region between them. In addition, we identify in the human locus two frequently occurring DNA polymorphisms which can be used to test the linkage of LD to known human dysmorphoses.
小鼠肢体畸形（ld）基因座位于小鼠的2号染色体上，会引发一种隐性遗传的典型肢体畸形/肾发育不全表型。在小鼠的这个基因座中，已鉴定出一个名为“formin”的基因，它在成年和胚胎组织中编码一系列经过不同加工的转录本。其中一组转录本在独立的突变小鼠ld等位基因中被破坏。我们希望报告通过序列比较和保守外显子的表达分离出一个与小鼠formin基因同源的人类基因组克隆。在分析的人类胎儿组织中，肾脏似乎是主要的表达位点。这个人类基因LD，在小鼠 - 人类体细胞杂种中定位于15号染色体q11 ---- qter，具体通过染色体原位杂交定位于15q13 ---- q14。这种定位确定了LD和β2 - 微球蛋白在小鼠2号染色体和人类15号染色体上为同线基因，并暗示它们之间区域的种间保守性。此外，我们在人类基因座中鉴定出两种常见的DNA多态性，可用于检测LD与已知人类畸形的连锁关系。
