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Investigates the variation of mtDNA among the eskimos in Greenland. Assessment on the improvement of genetic characterization of eskimos; Application of genetic dating to uncover the pre-history of eskimos; Identification on the founder types of mtDNA.

Studies the characterization of genetic miscoding lesions caused by postmortem damage. Key issues of interest; Analysis of pertinent topics and relevant issues; Implications on human genetics.

Studies the distribution patterns of postmortem damage in human mitochondrial DNA. Key issues of interest; Analysis of pertinent topics and relevant issues; Implications on human genetics.

The spectrum of postmortem damage in mitochondrial DNA was analyzed in a large data set of cloned sequences from ancient human specimens. The most common forms of damage observed are two complementary groups of transitions, termed "type 1" (adenine-->guanine/thymine-->cytosine) and "type 2" (cytosine-->thymine/guanine-->adenine). Single-primer extension PCR and enzymatic digestion with uracil-N-glycosylase confirm that each of these groups of transitions result from a single event, the deamination of adenine to hypoxanthine, and cytosine to uracil, respectively. The predominant form of transition-manifested damage varies by sample, though a marked bias toward type 2 is observed with increasing amounts of damage. The two transition types can be used to identify the original strand, light (L) or heavy (H), on which the initial damage event occurred, and this can increase the number of detected jumping-PCR artifacts by up to 80%. No bias toward H-strand-specific damage events is noted within the hypervariable 1 region of human mitochondria, suggesting the rapid postmortem degradation of the secondary displacement (D-loop) H strand. The data also indicate that, as damage increases within a sample, fewer H strands retain the ability to act as templates for enzymatic amplification. Last, a significant correlation between archaeological site and sample-specific level of DNA damage was detected.

The distribution of postmortem damage in mitochondrial DNA retrieved from 37 ancient human DNA samples was analyzed by cloning and was compared with a selection of published animal data. A relative rate of damage (rho(v)) was calculated for nucleotide positions within the human hypervariable region 1 (HVR1) and cytochrome oxidase subunit III genes. A comparison of damaged sites within and between the regions reveals that damage hotspots exist and that, in the HVR1, these correlate with sites known to have high in vivo mutation rates. Conversely, HVR1 subregions with known structural function, such as MT5, have lower in vivo mutation rates and lower postmortem-damage rates. The postmortem data also identify a possible functional subregion of the HVR1, termed "low-diversity 1," through the lack of sequence damage. The amount of postmortem damage observed in mitochondrial coding regions was significantly lower than in the HVR1, and, although hotspots were noted, these did not correlate with codon position. Finally, a simple method for the identification of incorrect archaeological haplogroup designations is introduced, on the basis of the observed spectrum of postmortem damage.