一例东北马鹿白化病的病例分析

A Case of Albinismin a Dongbei Wapiti

为了探究一只东北马鹿的白化病的遗传机制,对其进行了30全基因组重测序及生物信息分析并进行验证。结果表明。通过筛选与白化病致病基因相关的SNPs,最终定位到这只白化马鹿的5个SNPs,分别涉及到HPS3(c.A1652G),LYST(c.C3338T、c.G3635A、c.C4613T),TYR(c.C1204T)3个基因。同源蛋白序列分析排除了HPS3和LYST上突变位点的致病性,而TYR基因上为终止突变。RT-PCR分析进一步证实TYR基因的终止突变,蛋白结构预测分析显示,TYR基因的突变位点位于蛋白的胞质区与跨膜区之间,而作为与网格衔接蛋白AP-3接合的双亮氨酸基序(EEXXXPLL)位于膜内区,因突变而丢失。综上分析,TYR基因(c.C1204T)突变导致了马鹿的白化病。该突变使TYR尾端丢失,包含了双亮氨酸基序和跨膜区丢失,TYR蛋白无法从内质网转移到黑素体上,黑素体功能性缺失导致白化病。

To investigate the genetic mechanismof albinismin this Dongbei Wapiti,30 whole genome resequencing,bioinformatic analysis,and validation were performed on this Dongbei Wapiti.Data screening for SNPs associated with albino pathogenicity genes finally localized five SNPs in this albino wapiti,which were HPS3(c.A1652G),LYST(c.C3338T,c.G3635A,c.C4613T)and TYR(c.C1204T),with a termination mutation on the TYR gene.Homologous protein sequence analysis excluded pathogenicity of the mutated sites on HPS3 and LYST.RT-PCR analysis further confirmed the termination mutation in the TYR gene,and structural prediction analysis of the TYR protein showed that the mutated site was located between the cytoplasmic and transmembrane structural domains of the protein,and that the di-leucine motif(EEXXXPLL),which serves as a splice to the lattice bridging protein AP-3,was located in the intramembrane.In summary,the base substitution(c.C1204T)on the TYR gene caused the albinism in this wapiti.This mutation results in the loss of the TYR tail,which contains the double leucine motif and the loss of the transmembrane region,preventing the transfer of TYR protein from the endoplasmic reticulumto the melanosome,and the functional loss of the melanosome leading to albinism.