Reflections of Our Past: How Human History Is Revealed in Our Genes

Reflections of Our Past: How Human History Is Revealed in Our Genes. John H. Relethford. Boulder: Westview Press, 2004. 257 pp.     

Chromosomal Mapping of the Human M6 Genes

M6 is a neuronal membrane glycoprotein that may have an important role in neural development. This molecule was initially defined by a monoclonal antibody that affected the survival of cultured cerebellar neurons and the outgrowth of neurites. The nature of the antigen was discovered by expression cDNA cloning using this monoclonal antibody. Two distinct murine M6 cDNAs (designated M6a and M6b) whose deduced amino acid sequences were remarkably similar to that of the myelin proteolipid protein were previously isolated. We have isolated partial human cDNA and genomic clones encoding M6a and M6b and have characterized them by restriction mapping, Southern hybridization with cDNA probes, and sequence analysis. We have localized these genes within the human genome by FISH (fluorescencein situhybridization). The human M6a gene is located at 4q34, and the M6b gene is located at Xp22.2. A number of human neurological disorders have been mapped to the Xp22 region, including Aicardi syndrome (MIM 304050), Rett syndrome (MIM 312750), X-linked Charcot–Marie–Tooth neuropathy (MIM 302801), and X-linked mental retardation syndromes (MRX1, MIM 309530). This raises the possibility that a defect in the M6b gene is responsible for one of these neurological disorders.     

Finding Protein-Coding Genes through Human Polymorphisms

Human gene catalogs are fundamental to the study of human biology and medicine. But they are all based on open reading frames (ORFs) in a reference genome sequence (with allowance for introns). Individual genomes, however, are polymorphic: their sequences are not identical. There has been much research on how polymorphism affects previously-identified genes, but no research has been done on how it affects gene identification itself. We computationally predict protein-coding genes in a straightforward manner, by finding long ORFs in mRNA sequences aligned to the reference genome. We systematically test the effect of known polymorphisms with this procedure. Polymorphisms can not only disrupt ORFs, they can also create long ORFs that do not exist in the reference sequence. We found 5,737 putative protein-coding genes that do not exist in the reference, whose protein-coding status is supported by homology to known proteins. On average 10% of these genes are located in the genomic regions devoid of annotated genes in 12 other catalogs. Our statistical analysis showed that these ORFs are unlikely to occur by chance.     

Linkage Disequilibrium Decay and Past Population History in the Human Genome

The fluctuation of population size has not been well studied in the previous studies of theoretical linkage disequilibrium (LD) expectation. In this study, an improved theoretical prediction of LD decay was derived to account for the effects of changes in effective population sizes. The equation was used to estimate effective population size (N_e) assuming a constant N_e and LD at equilibrium, and these N_e estimates implied the past changes of N_e for a certain number of generations until equilibrium, which differed based on recombination rate. As the influence of recent population history on the N_e estimates is larger than old population history, recent changes in population size can be inferred more accurately than old changes. The theoretical predictions based on this improved expression showed accurate agreement with the simulated values. When applied to human genome data, the detailed recent history of human populations was obtained. The inferred past population history of each population showed good correspondence with historical studies. Specifically, four populations (three African ancestries and one Mexican ancestry) showed population growth that was significantly less than that of other populations, and two populations originated from China showed prominent exponential growth. During the examination of overall LD decay in the human genome, a selection pressure on chromosome 14, the gephyrin gene, was observed in all populations.     

High-Resolution Mapping of Ribosomal Protein Genes to Human Chromosome 19

In a systematic effort for mapping of all the human ribosomalprotein (rp) genes, we have found that an unusually large number(12) of rp genes are present on chromosome 19 and subsequentlydetermined their locations on the chromosome by a radiation-hybridprocedure. For this, we isolated cosmid clones correspondingto each gene and placed nine of them on a metric physical mapof chromosome 19. Although most genes are scattered over thechromosome, we found three genes are clustered in a 0.6-Mb regionat 19q13.3 and two of them, RPL13A and RPS11, within a singlecosmid only 4.3 kb apart. To explore a possible relationshipbetween rp gene defects and human disease, we compared map positionsof the rpgenes and disease loci on chromosome 19, which ledus to find RPS9 gene in the same interval as the gene for retinitispigmentosa 11. The disease locus has previously been mappedto the 6-cM interval at 19q13.4 between markers D19S572 andD19S926, which corresponds to less than 2-Mb region on the metricphysical map. We mapped RPS9 about 800 kb distal to D19S572.     

Mapping Small-World Properties through Development in the Human Brain: Disruption in Schizophrenia

Evidence from imaging studies suggests that the human brain has a small-world network topology that might be disrupted in certain brain disorders. However, current methodology is based on global graph theory measures, such as clustering, C, characteristic path length, L, and small-worldness, S, that lack spatial specificity and are insufficient to identify regional brain abnormalities. Here we propose novel ultra-fast methodology for mapping local properties of brain network topology such as local C, L and S (lC, lL and lS) in the human brain at 3-mm isotropic resolution from ‘resting-state’ magnetic resonance imaging data. Test-retest datasets from 40 healthy children/adolescents were used to demonstrate the overall good reliability of the measures across sessions and computational parameters (intraclass correlation > 0.5 for lC and lL) and their low variability across subjects (< 29%). Whereas regions with high local functional connectivity density (lFCD; local degree) in posterior parietal and occipital cortices demonstrated high lC and short lL, subcortical regions (globus pallidus, thalamus, hippocampus and amygdala), cerebellum (lobes and vermis), cingulum and temporal cortex also had high, lS, demonstrating stronger small-world topology than other hubs. Children/adolescents had stronger lFCD, higher lC and longer lL in most cortical regions and thalamus than 74 healthy adults, consistent with pruning of functional connectivity during maturation. In contrast, lFCD, lC and lL were weaker in thalamus and midbrain, and lL was shorter in frontal cortical regions and cerebellum for 69 schizophrenia patients than for 74 healthy controls, suggesting exaggerated pruning of connectivity in schizophrenia. Follow up correlation analyses for seeds in thalamus and midbrain uncovered lower positive connectivity of these regions in thalamus, putamen, cerebellum and frontal cortex (cingulum, orbitofrontal, inferior frontal) and lower negative connectivity in auditory, visual, motor, premotor and somatosensory cortices for schizophrenia patients than for controls, consistent with prior findings of thalamic disconnection in schizophrenia.     

Bioarchaeology of Spanish Florida: The Impact of Colonialism.; Skeletons in Our Closet: Revealing Our Past through Bioarchaeology.

Bioarchaeology of Spanish Florida: The Impact of Colonialism. Clark Spencer Larsen. ed. Gainsville: University Press of Florida, 2001. 320 pp.
Skeletons in Our Closet: Revealing Our Past through Bioarchaeology. Clark Spencer Larsen. Princeton: Princeton University Press, 2000. 248 pp.     

Voices of Our Past: Using Oral History to Explore Funds of Knowledge within a Puerto Rican Family

This article presents an educational rationale for using oral history to teach students that there are multiple sources of knowledge and ways to seek valid information. A case study to explore the funds of knowledge within an extended Puerto Rican family is used illustratively. The study describes the leadership role played by one grandmother as the family participated in multiple migrations, describes creative ways employed by her and other women to reestablish the community, and challenges some stereotypes of Latinas.