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Human mitochondrial dna polymorphisms, haplogroups, associations with physiological conditions, and genotyping arrays

机译:人类线粒体dna多态性,单倍型,与生理状况的关联以及基因分型阵列

摘要

This invention provides human mtDNA polymorphisms that are diagnostic of all the major human haplogroups and methods of diagnosing those haplogroups and selected subhaplogroups. This invention also provides methods for identifying evolutionarily significant mitochondrial DNA genes, nucleotide alleles, and amino acid alleles. Evolutionarily significant genes and alleles are identified using one or two populations of a single species. The process of identifying evolutionarily significant nucleotide alleles involves identifying evolutionarily significant genes and then evolutionarily significant nucleotide alleles in those genes, and identifying evolutionarily significant amino acid alleles involves identifying amino acids encoded by all nonsynonymous alleles. Synonymous codings of the nucleotide alleles encoding evolutionarily significant amino acid alleles of this invention are equivalent to the evolutionarily significant amino acid alleles disclosed herein and are included within the scope of this invention. Synonymous codings include alleles at neighboring nucleotide loci that are within the same codon. This invention also provides methods for associating haplogroups and evolutionarily significant nucleotide and amino acid alleles with predispositions to physiological conditions. Methods for diagnosing predisposition to LHON, and methods for diagnosing increased likelihood of developing blindness, centenaria, and increased longevity that are not dependent on the geographical location of the individual being diagnosed are provided herein. Diagnosis of an individual with a predisposition to an energy metabolism-related physiological condition is dependent on the geographic region of the individual. Physiological conditions diagnosable by the methods of this invention include healthy conditions and pathological conditions. Physiological conditions that are associated with haplogroups and with alleles provided by this invention include energetic imbalance, metabolic disease, abnormal energy metabolism, abnormal temperature regulation, abnormal oxidative phosphorylation, abnormal electron transport, obesity, amount of body fat, diabetes, hypertension, and cardiovascular disease.
机译:本发明提供了诊断所有主要人类单倍型的人类mtDNA多态性和诊断那些单倍型和选择的亚单倍型的方法。本发明还提供了鉴定具有进化意义的线粒体DNA基因,核苷酸等位基因和氨基酸等位基因的方法。使用单个物种的一个或两个种群鉴定具有进化重要性的基因和等位基因。鉴定具有进化意义的核苷酸等位基因的过程包括鉴定具有进化意义的基因,然后鉴定那些基因中具有进化意义的核苷酸等位基因,而鉴定具有进化意义的氨基酸等位基因则涉及鉴定所有非同义等位基因编码的氨基酸。编码本发明的进化上重要的氨基酸等位基因的核苷酸等位基因的同义编码等同于本文公开的进化上重要的氨基酸等位基因,并且包括在本发明的范围内。同义编码包括在相同密码子内的相邻核苷酸基因座处的等位基因。本发明还提供了将单倍群和进化上重要的核苷酸和氨基酸等位基因与易患生理状况相关联的方法。本文提供了不依赖于被诊断个体地理位置的诊断LHON易感性的方法,以及诊断失明,百分率增加和寿命延长的方法。具有能量代谢相关生理状况易感性的个体的诊断取决于个体的地理区域。通过本发明的方法可诊断的生理状况包括健康状况和病理状况。本发明提供的与单倍群和等位基因有关的生理条件包括能量失衡,代谢疾病,异常能量代谢,温度调节异常,氧化磷酸化异常,电子运输异常,肥胖症,体脂肪量,糖尿病,高血压和心血管疾病疾病。

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