Fine mapping of dental fluorosis quantitative trait loci in mice.

Fine mapping of dental fluorosis quantitative trait loci in mice.
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DOI:
10.1111/j.1600-0722.2011.00868.x
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发表时间:
2011-12
影响因子:
1.9
通讯作者:
Zou F
Zou F
中科院分区:
医学4区
文献类型:
--
作者:
Everett ET;Yin Z;Yan D;Zou F

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遗传因素是氟斑牙(DF)易感性/耐药性的基础。A/J(DF敏感)和129 P3/J(DF抗性)菌株先前已被用于检测与DF相关的染色体(Chr)2和11上的数量性状位点(QTL)。在本研究中,增加标记密度基因分型,然后进行区间作图,以缩小QTL的间隔,提高LOD评分。当LOD ≥ 6.0时,Chr 2的间隔较窄(57-84 cM或~51 Mb),LOD ≥ 7.0(62-79 cM或~32 Mb),LOD ≥ 8.0(65-74 cM或~17 Mb);在Chr 11上,LOD ≥ 6.0时,检测区间为18-51 cM(~53 Mb),LOD ≥ 7.0(28-48 cM或~34 Mb),LOD ≥ 8.0(31-45 cM或~22 Mb)。A/J和129 P3/J之间的单倍型分析进一步缩小了QTL间隔。Accn 1是根据其在Chr 11上的LOD值峰值附近的位置和与C.线虫抗氟基因flr 1 Accn 1 −/−和野生型小鼠之间的DF严重程度没有差异。ACCN 1功能的丧失不会改变小鼠DF的严重程度。缩小DF QTL间隔将有助于额外的候选基因选择和询问。
Genetic factors underlie dental fluorosis (DF) susceptibility/resistance. The A/J (DF susceptible) and 129P3/J (DF resistant) strains have been previously used to detect quantitative trait loci (QTL) associated with DF on chromosomes (Chr) 2 and 11. In the present study increased marker density genotyping followed by interval mapping was performed to narrow the QTL intervals and improve the LOD scores. Narrower intervals on Chr 2 where LOD ≥ 6.0 (57–84 cM or ~51 Mb), LOD ≥ 7.0 (62–79 cM or ~32 Mb), and LOD ≥ 8.0 (65–74 cM or ~17 Mb); and on Chr 11 where LOD ≥ 6.0 the interval was 18–51 cM (~53 Mb), LOD ≥ 7.0 (28–48 cM or ~34 Mb), and LOD ≥ 8.0 (31–45 cM or~22 Mb) were obtained. Haplotype analysis between A/J and 129P3/J further reduced QTL intervals. Accn1 was selected as a candidate gene based upon its location near the peak LOD score on Chr 11 and distant homology with the C. elegans fluoride resistance gene flr1. DF severity between Accn1−/− and wildtype mice was not different. The loss of ACCN1 function does not modify DF severity in mice. Narrowing the DF QTL intervals will facilitate additional candidate gene selections and interrogation.
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