Guziewicz K E, Owczarek-Lipska M, Küffer J, Schelling C, Tontis A, Denis C, Eggen A, Leeb T, Dolf G, Braunschweig M H
Department of Clinical Studies-Philadelphia, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Anim Genet. 2007 Jun;38(3):265-9. doi: 10.1111/j.1365-2052.2007.01596.x. Epub 2007 Apr 13.
Bovine dilated cardiomyopathy (BDCMP) is a severe and terminal disease of the heart muscle observed in Holstein-Friesian cattle over the last 30 years. There is strong evidence for an autosomal recessive mode of inheritance for BDCMP. The objective of this study was to genetically map BDCMP, with the ultimate goal of identifying the causative mutation. A whole-genome scan using 199 microsatellite markers and one SNP revealed an assignment of BDCMP to BTA18. Fine-mapping on BTA18 refined the candidate region to the MSBDCMP06-BMS2785 interval. The interval containing the BDCMP locus was confirmed by multipoint linkage analysis using the software loki. The interval is about 6.7 Mb on the bovine genome sequence (Btau 3.1). The corresponding region of HSA19 is very gene-rich and contains roughly 200 genes. Although telomeric of the marker interval, TNNI3 is a possible positional and a functional candidate for BDCMP given its involvement in a human form of dilated cardiomyopathy. Sequence analysis of TNNI3 in cattle revealed no mutation in the coding sequence, but there was a G-to-A transition in intron 6 (AJ842179:c.378+315G>A). The analysis of this SNP using the study's BDCMP pedigree did not conclusively exclude TNNI3 as a candidate gene for BDCMP. Considering the high density of genes on the homologous region of HSA19, further refinement of the interval on BTA18 containing the BDCMP locus is needed.
牛扩张型心肌病（BDCMP）是过去30年在荷斯坦-弗里生奶牛中观察到的一种严重的终末期心肌疾病。有强有力的证据表明BDCMP呈常染色体隐性遗传模式。本研究的目的是对BDCMP进行基因定位，最终目标是确定致病突变。使用199个微卫星标记和一个单核苷酸多态性（SNP）进行的全基因组扫描显示，BDCMP定位于牛18号染色体（BTA18）。在BTA18上进行精细定位将候选区域缩小到MSBDCMP06-BMS2785区间。使用软件loki通过多点连锁分析确认了包含BDCMP基因座的区间。该区间在牛基因组序列（Btau 3.1）上约为6.7兆碱基对（Mb）。人类19号染色体（HSA19）的相应区域基因非常丰富，大约包含200个基因。尽管TNNI3位于标记区间的端粒侧，但鉴于其与一种人类扩张型心肌病有关，它是BDCMP的一个可能的位置候选基因和功能候选基因。牛TNNI3的序列分析显示编码序列中没有突变，但内含子6中有一个G到A的转换（AJ842179:c.378+315G>A）。使用本研究的BDCMP家系对该SNP进行分析并没有确凿地排除TNNI3作为BDCMP候选基因的可能性。考虑到HSA19同源区域的基因高密度，需要进一步缩小BTA18上包含BDCMP基因座的区间。
