Le Roy I, Perez-Diaz F, Cherfouh A, Roubertoux P L
UPR CNRS 9074 Génétique, Neurogénétique, Comportement Institut de Transgénose, Orléans, France.
Dev Psychobiol. 1999 Mar;34(2):139-58. doi: 10.1002/(sici)1098-2302(199903)34:2<139::aid-dev7>3.0.co;2-h.
Chromosomal mapping of genes linked with 19 measures of sensorial, motor, and body weight development were investigated. Chromosomal mapping is the first step towards gene identification. When a genomic region is shown to be linked to a trait, it is possible to select a reduced number of candidate genes that have been previously mapped on this region. The involvement of every gene can be individually tested either by molecular (transgenesis, homologous recombination) or traditional methods (congenicity). Mapping was performed using 389 males and females from two inbred strains of laboratory mice C57BL/6By and NZB/BlNJ, their reciprocal F1s and F2s. Thirty-six Quantitative Trait Loci (QTL) were mapped, 12 reached the 3.13 lod score, being thus considered as confirmed. These QTL were tentatively labeled: Cliff Drop Aversion (Cliff Qtl), Geotaxia (Geot Qtl), Vertical Clinging (VertCling Qtl), Bar Holding with the 4 paws (BH4P Qtl), Age at Eyelid Opening (Aeyo Qtl), Visual Placing (Vispl Qtl), Startle Response (Start Qtl1, Start Qtl2), Body Weight at Day 10 in Males pooled with Females (Bwefmd10 Qtl), and Body Weight at Day 30 in males (Bwemd30 Qtl). For the majority of the developmental measures, the QTL that were mapped contributed little to the phenotypic variance, even when mitochondrial DNA contribution was included: Righting Response (12.7%), Cliff Drop Aversion (10%), Crossed Extensor Response (18.1%), Geotaxia (16.2%), Bar Holding Response for 10 s (12.1%), Bar Holding Response with 4 paws (8.1%), Vertical Clinging (9.3%), Vertical Climbing (5%), Startle Response (21.2%), Eyelid Opening (14.6%), Visual Placing (22%), Body Weight at Day 10 (27%), Body Weight at Day 15 in Females (52.5%), Body Weight at Day 15 in Males (17%), Body Weight at Day 30 in Females (42%), and Body Weight at Day 30 in Males (48%). A factorial analysis of the correlations between the measures of development did not provide evidence of a general factor. A general genetic factor of development was also rejected because few common genetic correlates were discovered for the 19 measures of development (Body Weight at Days 15 and 30 in Females on Chromosome 2, Eyelid Opening and Body Weight at Day 10 on Chromosome 5 and mitochondrial genome for five measures). Co-identification of genes, the function of which were previously known thanks to newly discovered QTL, should help to explain the function of QTL. Present data help to highlight candidate regions including several genes that could be candidates for the QTL function. Large confidence intervals were obtained as usual from the F2 intercrossed population. More stringent methods are suggested for more efficient co-identification.
研究了与19种感觉、运动和体重发育指标相关基因的染色体定位。染色体定位是基因识别的第一步。当一个基因组区域被证明与某一性状相关联时，就有可能筛选出先前已定位在该区域的数量较少的候选基因。每个基因的参与情况可以通过分子方法（转基因、同源重组）或传统方法（同基因性）单独进行检测。使用来自两个近交系实验小鼠C57BL/6By和NZB/BlNJ的389只雄性和雌性小鼠、它们的正反交F1代和F2代进行定位。共定位了36个数量性状基因座（QTL），其中12个达到了3.13的lod分数，因此被认为得到了确认。这些QTL被暂时标记为：悬崖躲避（Cliff Qtl）、地趋性（Geot Qtl）、垂直附着（VertCling Qtl）、四爪抓杆（BH4P Qtl）、睁眼年龄（Aeyo Qtl）、视觉定位（Vispl Qtl）、惊吓反应（Start Qtl1、Start Qtl2）、雄性和雌性合并的第10天体重（Bwefmd10 Qtl）以及雄性第30天体重（Bwemd30 Qtl）。对于大多数发育指标，即使包括线粒体DNA的贡献，所定位的QTL对表型变异的贡献也很小：翻正反应（12.7%）、悬崖躲避（10%）、交叉伸展反应（18.1%）、地趋性（16.2%）、10秒抓杆反应（12.1%）、四爪抓杆反应（8.1%）、垂直附着（9.3%）、垂直攀爬（5%）、惊吓反应（21.2%）、睁眼（14.6%）、视觉定位（22%）、第10天体重（27%）、雌性第15天体重（52.5%）、雄性第15天体重（17%）、雌性第30天体重（42%）以及雄性第30天体重（48%）。对发育指标之间的相关性进行的因子分析没有提供存在一般因子的证据。一个发育的一般遗传因子也被否定了，因为在19个发育指标中几乎没有发现共同的遗传相关性（雌性第15天和第30天体重在2号染色体上，睁眼和第10天体重在5号染色体上，以及线粒体基因组与5个指标相关）。对其功能因新发现的QTL而先前已知的基因进行共同鉴定，应该有助于解释QTL的功能。目前的数据有助于突出包括几个可能是QTL功能候选基因的候选区域。像往常一样，从F2杂交群体中获得了较大的置信区间。建议采用更严格的方法以进行更有效的共同鉴定。
