3-Hydroxy-3-methylglutaryl-coenzyme A lyase deficiency: initial presentation in a young adult.

3-Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) lyase deficiency is a rare inborn error affecting leucine catabolism and ketogenesis, usually presenting in the neonatal period. Late forms of the disease have been detected in infancy and childhood, but not in adults. We report a case of HMG-CoA lyase deficiency with initial presentation in a 29-year-old adult with no prior history of the disease, which to our knowledge is the first case described with presentation at this age.

Y-chromosomal diversity in Europe is clinal and influenced primarily by geography, rather than by language.

Clinal patterns of autosomal genetic diversity within Europe have been interpreted in previous studies in terms of a Neolithic demic diffusion model for the spread of agriculture; in contrast, studies using mtDNA have traced many founding lineages to the Paleolithic and have not shown strongly clinal variation. We have used 11 human Y-chromosomal biallelic polymorphisms, defining 10 haplogroups, to analyze a sample of 3,616 Y chromosomes belonging to 47 European and circum-European populations. Patterns of geographic differentiation are highly nonrandom, and, when they are assessed using spatial autocorrelation analysis, they show significant clines for five of six haplogroups analyzed. Clines for two haplogroups, representing 45% of the chromosomes, are continentwide and consistent with the demic diffusion hypothesis. Clines for three other haplogroups each have different foci and are more regionally restricted and are likely to reflect distinct population movements, including one from north of the Black Sea. Principal-components analysis suggests that populations are related primarily on the basis of geography, rather than on the basis of linguistic affinity. This is confirmed in Mantel tests, which show a strong and highly significant partial correlation between genetics and geography but a low, nonsignificant partial correlation between genetics and language. Genetic-barrier analysis also indicates the primacy of geography in the shaping of patterns of variation. These patterns retain a strong signal of expansion from the Near East but also suggest that the demographic history of Europe has been complex and influenced by other major population movements, as well as by linguistic and geographic heterogeneities and the effects of drift.

Genetic diversity in the Iberian Peninsula determined from mitochondrial sequence analysis.

We have analysed 302 bp of the first hypervariable region of the mitochondrial D-loop in 271 individuals from different regions of the Iberian Peninsula and 85 individuals from Algeria. The Basque population is significantly different from neighbouring populations in terms of overall levels of diversity. This is because the majority of sequences in the Basques are restricted to the lineage group defined by the CRS (Cambridge Reference Sequence) and its derivatives although, like other Iberian populations, they showed a unimodal distribution of pairwise sequence differences. The timing of divergence of populations within Iberia points to a shared ancestry of all populations in the Upper Palaeolithic. Further genetic subdivision is apparent in Catalonia and Andalusia, with increased genetic diversity in the latter. Lineage diversity comparisons of Iberian populations with European (Tuscan) and North African (Algerian) populations shows the Iberian Peninsula to be more similar to other European populations, although a small number of Iberian lineages can be traced to North Africa.

Paleolithic and neolithic lineages in the European mitochondrial gene pool.

Phylogenetic and diversity analysis of the mtDNA control region sequence variation of 821 individuals from Europe and the Middle East distinguishes five major lineage groups with different internal diversities and divergence times. Consideration of the diversities and geographic distribution of these groups within Europe and the Middle East leads to the conclusion that ancestors of the great majority of modern, extant lineages entered Europe during the Upper Paleolithic. A further set of lineages arrived from the Middle East much later, and their age and geographic distribution within Europe correlates well with archaeological evidence for two culturally and geographically distinct Neolithic colonization events that are associated with the spread of agriculture. It follows from this interpretation that the major extant lineages throughout Europe predate the Neolithic expansion and that the spread of agriculture was a substantially indigenous development accompanied by only a relatively minor component of contemporary Middle Eastern agriculturalists. There is no evidence of any surviving Neanderthal lineages among modern Europeans.