Danciger Michael, Lyon Jessica, Worrill Danielle, LaVail Matthew M, Yang Haidong
Department of Biology, Loyola Marymount University, Los Angeles, California 90045-2959, USA.
Invest Ophthalmol Vis Sci. 2003 Jun;44(6):2442-9. doi: 10.1167/iovs.02-1252.
BALB/cByJ (C) albino mice have significantly more retinal degeneration as they age than C57BL/6J-c(2J) (B6) albinos. To discover the genetic loci that influence age-related retinal degeneration (ARD), a quantitative genetics study was performed with 8-month-old progeny from an intercross between these two strains.
The thickness of the outer nuclear layer of the retina was used as the quantitative trait. A genome-wide scan was performed with 86 genetic markers at an average distance of 15.7 cM. Map Manager QTX was used to analyze the data.
Three highly significant quantitative trait loci (QTLs) were detected on mouse chromosomes (Chrs) 6, 10, and 16. The B6 alleles were protective against ARD in the first two, and the C allele was protective in the third. Several suggestive, weak QTLs were also found, along with a gender-related effect. The strongest and most highly significant QTL on Chr 6 accounted for 30% of the total genetic effect with a LOD score of 13.5. The RPE65/MET450 variant of major influence on constant light-induced retinal degeneration (LRD) in a previous study of these same two mouse strains had no influence on ARD, and only some of the weak, suggestive QTLs influencing ARD were also observed in LRD.
Because none of the ARD QTLs was homologous to human chromosomal loci so far implicated in age-related macular degeneration, each represents a new candidate gene for potential study. The gene represented by the Chr 6 QTL is of particular interest because it has broad influence, very high significance, and a B6 allele that protects against ARD.
与C57BL/6J-c(2J)（B6）白化小鼠相比，BALB/cByJ（C）白化小鼠随着年龄增长视网膜变性更为显著。为了发现影响年龄相关性视网膜变性（ARD）的基因位点，对这两个品系杂交产生的8月龄后代进行了一项数量遗传学研究。
将视网膜外核层厚度用作数量性状。使用86个遗传标记进行全基因组扫描，平均间距为15.7 cM。使用Map Manager QTX分析数据。
在小鼠6号、10号和16号染色体上检测到3个高度显著的数量性状基因座（QTL）。在前两个QTL中，B6等位基因对ARD具有保护作用，在第三个QTL中，C等位基因具有保护作用。还发现了几个暗示性的、较弱的QTL，以及一个与性别相关的效应。6号染色体上最强且最显著的QTL占总遗传效应的30%，LOD得分为13.5。在先前对这两个相同小鼠品系的研究中，对持续光诱导视网膜变性（LRD）有主要影响的RPE65/MET450变体对ARD没有影响，并且在LRD中仅观察到一些影响ARD的较弱的、暗示性的QTL。
由于目前尚未发现与年龄相关性黄斑变性相关的人类染色体位点与任何ARD QTL同源，因此每个ARD QTL都代表一个潜在研究的新候选基因。6号染色体QTL所代表的基因特别值得关注，因为它具有广泛的影响、非常高的显著性，并且其B6等位基因对ARD具有保护作用。
