Homozygosity haplotype allows a genomewide search for the autosomal segments shared among patients

A promising strategy for identifying disease susceptibility genes for both single- and multiple-gene diseases is to search patients' autosomes for shared chromosomal segments derived from a common ancestor. Such segments are characterized by the distinct identity of their haplotype. The methods and algorithms currently available have only a limited capability for determining a high-resolution haplotype genomewide. We herein introduce the homozygosity haplotype (HH), a haplotype described by the homozygous SNPs that are easily obtained from high-density SNP genotyping data. The HH represents haplotypes of both copies of homologous autosomes, allowing for direct comparisons of the autosomes among multiple patients and enabling the identification of the shared segments. The HH successfully detected the shared segments from members of a large family with Marfan syndrome, which is an autosomal dominant, single-gene disease. It also detected the shared segments from patients with model multigene diseases originating with common ancestors who lived 10-25 generations ago. The HH is therefore considered to be useful for the identification of disease susceptibility genes in both single- and multiple-gene diseases.     

Mouse SWAM1 and SWAM2 are antibacterial proteins composed of a single whey acidic protein motif

Antibacterial proteins are important participants in the innate immunity system. Elafin and SLPI are the whey acidic protein (WAP) motif proteins with both antibacterial activity and antiprotease activity, and their role in innate immunity is under intense investigation. We cloned two novel antibacterial WAP motif proteins from mice, SWAM1 and SWAM2. SWAM1 and SWAM2 are composed of a signal sequence and a single WAP motif that has high homologies with the WAP motifs of elafin and SLPI. SWAM1 is constitutively expressed in kidney and epididymis, and is induced in the pneumonic lung. SWAM2 is constitutively expressed in tongue. SWAM1 and SWAM2 inhibit the growth of both Escherichia coli and Staphylococcus aureus at a IC(90) (concentration that achieves 90% inhibition) of 10 microM. Human genes LOC149709 and huWAP2 are considered to be human SWAM1 and SWAM2, respectively. These and several WAP motif proteins (WAP1, elafin, SLPI, HE4, eppin, C20orf170, LOC164237, and WFDC3) form a gene cluster on human chromosome 20, suggesting that they may be derived from the same ancestral gene by gene duplication. Our results underscore the role of the WAP motif as a skeletal motif to form antibacterial proteins, and warrant the study of antibacterial activity in other WAP motif proteins.     

利用传递不平衡分析在多群体中鉴别猪脐疝易感基因

在本实验室前期利用白色杜洛克×二花脸F₂资源家系开展脐疝易感位点全基因组扫描定位的基础上,文章在7号染色体上的SWR1928和10号染色体上的SW830易感标记区域,结合脐疝发病机制在多群体中进行脐疝位置功能候选基因的筛选和易感位点的精细定位。在两个显著关联的微卫星位点区域搜寻到12个位置功能候选基因,采用比较测序法,选取12个候选基因内共计40个SNP位点在白色杜洛克×二花脸资源家系F₂/F₃脐疝群体中进行基因分型,利用Plink v1.07软件对基因型数据进行质量控制和传递不平衡(Transmission disequilibrium test,TDT)分析。结果表明,IL16(Interleukin 16)基因中的g.708C>T位点和CDC73(Cell division cycle 73)基因中的g.10664G>A位点与脐疝的关联性达到显著水平(P<0.05)。对这两个位点在西方商业猪种脐疝患病家系中进行基因分型和TDT验证分析,发现CDC73基因中的g.10664G>A位点仍与猪脐疝呈显著关联(P<0.05)。同时对CDC73基因中与资源家系脐疝呈弱相关的两个SNP位点g.10546A>G和g.10811A>G在西方商业猪种中进行TDT验证分析,发现这两个SNP位点与商业猪种脐疝发生的关联性达到极显著水平(P<0.01)。根据文章的分析结果,结合脐疝发生的生理机制及CDC73基因的生物学功能,推测CDC73基因可能为猪脐疝发生的易感基因。