Haplogroup effects and recombination of mitochondrial DNA: Novel clues from the analysis of Leber hereditary optic neuropathy pedigrees
Haplogroup effects and recombination of mitochondrial DNA: Novel clues from the analysis of Leber hereditary optic neuropathy pedigrees
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DOI：
10.1086/501236
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发表时间：
2006-04-01
影响因子：
9.8
通讯作者：
Torroni, A
中科院分区：
文献类型：
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作者：
Carelli, V;Achilli, A;Torroni, A
对意大利连续诊断的87例Leber遗传性视神经病变(LHON)患者的线粒体DNA(MtDNA)进行了详细的分析，其中包括一个极大的巴西意大利母系家庭。只观察到7对和3对相同的单倍型，证明绝大多数LHON突变是由独立的突变事件引起的。将突变事件分配到单倍群中证实了J1和J2在LHON表达中发挥作用，但缩小了与J1c和J2b亚类的关联，从而表明细胞色素b中两种特定的氨基酸组合变化是mtDNA背景效应的原因，这可能发生在呼吸链复合体I和III形成的超复合体水平上。对具有相同单倍型的家系进行了家系重新研究，这导致了三对家系的重新连接，包括巴西家系和意大利家系。对重新连接的家族的整个mtDNA样本的测序证实了家系重建，但显示巴西家族在两个控制区位置上是异质性的。对12名巴西受试者的这两个位点的调查显示，大多数情况下存在三质体，但没有证据表明线粒体DNA重组会出现四质体。
The mitochondrial DNA ( mtDNA) of 87 index cases with Leber hereditary optic neuropathy ( LHON) sequentially diagnosed in Italy, including an extremely large Brazilian family of Italian maternal ancestry, was evaluated in detail. Only seven pairs and three triplets of identical haplotypes were observed, attesting that the large majority of the LHON mutations were due to independent mutational events. Assignment of the mutational events into haplogroups confirmed that J1 and J2 play a role in LHON expression but narrowed the association to the subclades J1c and J2b, thus suggesting that two specific combinations of amino acid changes in the cytochrome b are the cause of the mtDNA background effect and that this may occur at the level of the supercomplex formed by respiratory-chain complexes I and III. The families with identical haplotypes were genealogically reinvestigated, which led to the reconnection into extended pedigrees of three pairs of families, including the Brazilian family with its Italian counterpart. The sequencing of entire mtDNA samples from the reconnected families confirmed the genealogical reconstruction but showed that the Brazilian family was heteroplasmic at two control-region positions. The survey of the two sites in 12 of the Brazilian subjects revealed triplasmy in most cases, but there was no evidence of the tetraplasmy that would be expected in the case of mtDNA recombination.