Molecular markers and human history: A tale of two haplogroup systems

To chronicle demographic movement across African Asian corridors, a variety of molecular (sequence analysis, restriction mapping and denaturing high performance liquid chromatography etc.) and statistical (correspondence analysis, AMOVA, calculation of diversity indices and phylogenetic inference, etc.) techniques were employed to assess the phylogeographic patterns of mtDNA control region and Y chromosomal variation among 14 sub-Saharan, North African and Middle Eastern populations. The patterns of genetic diversity revealed evidence of multiple migrations across several African Asian passageways as well within the African continent itself. The two-part analysis uncovered several interesting results which include the following: (1) a north (Egypt and Middle East Asia) to south (sub-Saharan Africa) partitioning of both mtDNA and Y chromosomal haplogroup diversity, (2) a genetic diversity gradient in sub-Saharan Africa from east to west, (3) evidence in favor of the Levantine Corridor over the Horn of Africa as the major genetic conduit since the Last Glacial Maximum, (4) a substantially higher mtDNA versus Y chromosomal sub-Saharan component in the Middle East collections, (5) a higher representation of East versus West African mtDNA haplotypes in the Arabian Peninsula populations versus no such bias in the Levant groups and lastly, (6) genetic remnants of the Bantu demographic expansion in sub-Saharan Africa. ^

Human Synaptic Plasticity Gene Expression Profile and Dendritic Spine Density Changes in HIV-Infected Human CNS Cells: Role in HIV-Associated Neurocognitive Disorders (HAND)

HIV-associated neurocognitive disorders (HAND) is characterized by development of cognitive, behavioral and motor abnormalities, and occur in approximately 50% of HIV infected individuals. Our current understanding of HAND emanates mainly from HIV-1 subtype B (clade B), which is prevalent in USA and Western countries. However very little information is available on neuropathogenesis of HIV-1 subtype C (clade C) that exists in Sub-Saharan Africa and Asia. Therefore, studies to identify specific neuropathogenic mechanisms associated with HAND are worth pursuing to dissect the mechanisms underlying this modulation and to prevent HAND particularly in clade B infection. In this study, we have investigated 84 key human synaptic plasticity genes differential expression profile in clade B and clade C infected primary human astrocytes by using RT2 Profile PCR Array human Synaptic Plasticity kit. Among these, 31 and 21 synaptic genes were significantly (≥3 fold) down-regulated and 5 genes were significantly (≥3 fold) up-regulated in clade B and clade C infected cells, respectively compared to the uninfected control astrocytes. In flow-cytometry analysis, down-regulation of postsynaptic density and dendrite spine morphology regulatory proteins (ARC, NMDAR1 and GRM1) was confirmed in both clade B and C infected primary human astrocytes and SK-N-MC neuroblastoma cells. Further, spine density and dendrite morphology changes by confocal microscopic analysis indicates significantly decreased spine density, loss of spines and decreased dendrite diameter, total dendrite and spine area in clade B infected SK-N-MC neuroblastoma cells compared to uninfected and clade C infected cells. We have also observed that, in clade B infected astrocytes, induction of apoptosis was significantly higher than in the clade C infected astrocytes. In conclusion, this study suggests that down-regulation of synaptic plasticity genes, decreased dendritic spine density and induction of apoptosis in astrocytes may contribute to the severe neuropathogenesis in clade B infection.