36 research outputs found
Rare Copy Number Deletions Predict Individual Variation in Intelligence
Phenotypic variation in human intellectual functioning shows substantial heritability, as demonstrated by a long history of behavior genetic studies. Many recent molecular genetic studies have attempted to uncover specific genetic variations responsible for this heritability, but identified effects capture little variance and have proven difficult to replicate. The present study, motivated an interest in “mutation load” emerging from evolutionary perspectives, examined the importance of the number of rare (or infrequent) copy number variations (CNVs), and the total number of base pairs included in such deletions, for psychometric intelligence. Genetic data was collected using the Illumina 1MDuoBeadChip Array from a sample of 202 adult individuals with alcohol dependence, and a subset of these (N = 77) had been administered the Wechsler Abbreviated Scale of Intelligence (WASI). After removing CNV outliers, the impact of rare genetic deletions on psychometric intelligence was investigated in 74 individuals. The total length of the rare deletions significantly and negatively predicted intelligence (r = −.30, p = .01). As prior studies have indicated greater heritability in individuals with relatively higher parental socioeconomic status (SES), we also examined the impact of ethnicity (Anglo/White vs. Other), as a proxy measure of SES; these groups did not differ on any genetic variable. This categorical variable significantly moderated the effect of length of deletions on intelligence, with larger effects being noted in the Anglo/White group. Overall, these results suggest that rare deletions (between 5% and 1% population frequency or less) adversely affect intellectual functioning, and that pleotropic effects might partly account for the association of intelligence with health and mental health status. Significant limitations of this research, including issues of generalizability and CNV measurement, are discussed
The birth of a human-specific neural gene by incomplete duplication and gene fusion
Background: Gene innovation by duplication is a fundamental evolutionary process but is difficult to study in humans due to the large size, high sequence identity, and mosaic nature of segmental duplication blocks. The human-specific gene hydrocephalus-inducing 2, HYDIN2, was generated by a 364 kbp duplication of 79 internal exons of the large ciliary gene HYDIN from chromosome 16q22.2 to chromosome 1q21.1. Because the HYDIN2 locus lacks the ancestral promoter and seven terminal exons of the progenitor gene, we sought to characterize transcription at this locus by coupling reverse transcription polymerase chain reaction and long-read sequencing. Results: 5' RACE indicates a transcription start site for HYDIN2 outside of the duplication and we observe fusion transcripts spanning both the 5' and 3' breakpoints. We observe extensive splicing diversity leading to the formation of altered open reading frames (ORFs) that appear to be under relaxed selection. We show that HYDIN2 adopted a new promoter that drives an altered pattern of expression, with highest levels in neural tissues. We estimate that the HYDIN duplication occurred ~3.2 million years ago and find that it is nearly fixed (99.9%) for diploid copy number in contemporary humans. Examination of 73 chromosome 1q21 rearrangement patients reveals that HYDIN2 is deleted or duplicated in most cases. Conclusions: Together, these data support a model of rapid gene innovation by fusion of incomplete segmental duplications, altered tissue expression, and potential subfunctionalization or neofunctionalization of HYDIN2 early in the evolution of the Homo lineage
Large Tandem, Higher Order Repeats and Regularly Dispersed Repeat Units Contribute Substantially to Divergence Between Human and Chimpanzee Y Chromosomes
Comparison of human and chimpanzee genomes has received much attention,
because of paramount role for understanding evolutionary step distinguishing us
from our closest living relative. In order to contribute to insight into Y
chromosome evolutionary history, we study and compare tandems, higher order
repeats (HORs), and regularly dispersed repeats in human and chimpanzee Y
chromosome contigs, using robust Global Repeat Map algorithm. We find a new
type of long-range acceleration, human-accelerated HOR regions. In peripheral
domains of 35mer human alphoid HORs, we find riddled features with ten
additional repeat monomers. In chimpanzee, we identify 30mer alphoid HOR. We
construct alphoid HOR schemes showing significant human-chimpanzee difference,
revealing rapid evolution after human-chimpanzee separation. We identify and
analyze over 20 large repeat units, most of them reported here for the first
time as: chimpanzee and human ~1.6 kb 3mer secondary repeat unit (SRU) and
~23.5 kb tertiary repeat unit (~0.55 kb primary repeat unit, PRU); human 10848,
15775, 20309, 60910, and 72140 bp PRUs; human 3mer SRU (~2.4 kb PRU); 715mer
and 1123mer SRUs (5mer PRU); chimpanzee 5096, 10762, 10853, 60523 bp PRUs; and
chimpanzee 64624 bp SRU (10853 bp PRU). We show that substantial
human-chimpanzee differences are concentrated in large repeat structures, at
the level of as much as ~70% divergence, sizably exceeding previous numerical
estimates for some selected noncoding sequences. Smeared over the whole
sequenced assembly (25 Mb) this gives ~14% human--chimpanzee divergence. This
is significantly higher estimate of divergence between human and chimpanzee
than previous estimates.Comment: 22 pages, 7 figures, 12 tables. Published in Journal of Molecular
Evolutio
Copy number variation in the speciation of pigs: a possible prominent role for olfactory receptors
Background: Unraveling the genetic mechanisms associated with reduced gene flow between genetically differentiated populations is key to understand speciation. Different types of structural variations (SVs) have been found as a source of genetic diversity in a wide range of species. Previous studies provided detailed knowledge on the potential evolutionary role of SVs, especially copy number variations (CNVs), between well diverged species of e.g. primates. However, our understanding of their significance during ongoing speciation processes is limited due to the lack of CNV data from closely related species. The genus Sus (pig and its close relatives) which started to diverge ~4 Mya presents an excellent model for studying the role of CNVs during ongoing speciation. Results: In this study, we identified 1408 CNV regions (CNVRs) across the genus Sus. These CNVRs encompass 624 genes and were found to evolve ~2.5 times faster than single nucleotide polymorphisms (SNPs). The majority of these copy number variable genes are olfactory receptors (ORs) known to play a prominent role in food foraging and mate recognition in Sus. Phylogenetic analyses, including novel Bayesian analysis, based on CNVRs that overlap ORs retain the well-accepted topology of the genus Sus whereas CNVRs overlapping genes other than ORs show evidence for random drift and/or admixture. Conclusion: We hypothesize that inter-specific variation in copy number of ORs provided the means for rapid adaptation to different environments during the diversification of the genus Sus in the Pliocene. Furthermore, these regions might have acted as barriers preventing massive gene flow between these species during the multiple hybridization events that took place later in the Pleistocene suggesting a possible prominent role of ORs in the ongoing Sus speciation
L'Ureterectomia Segmentaria Con Anastomosi Termino-Terminale per Neoplasie Dell'Uretere Risultati a Distanza Di Tre Casi
Metabolic and Renal Complications and Immunologic Implications of Laparoscopic Urologic Surgery
Saarbruecker Diplomsoziologen in Ausbildung und Beruf eine empirische Untersuchung ueber die Absolventen des Saarbruecker Diplomstudienganges von 1969-1982
UuStB Koeln(38)-8406226 / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEDEGerman