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.
