Abstract:
:Recent studies have made great strides towards identifying putative genetic events underlying the evolution of the human brain and its emergent cognitive capacities. One of the most intriguing findings is the recurrent identification of adaptive evolution in genes associated with primary microcephaly, a developmental disorder characterized by severe reduction in brain size and intelligence, reminiscent of the early hominid condition. This has led to the hypothesis that the adaptive evolution of these genes has contributed to the emergence of modern human cognition. As with other candidate loci, however, this hypothesis remains speculative due to the current lack of methodologies for characterizing the evolutionary function of these genes in humans. Two primary microcephaly genes, ASPM and Microcephalin, have been implicated not only in the adaptive evolution of the lineage leading to humans, but in ongoing selective sweeps in modern humans as well. The presence of both the putatively adaptive and neutral alleles at these loci provides a unique opportunity for using normal trait variation within humans to test the hypothesis that the recent selective sweeps are driven by an advantage in cognitive abilities. Here, we report a large-scale association study between the adaptive alleles of these genes and normal variation in several measures of IQ. Five independent samples were used, totaling 2393 subjects, including both family-based and population-based datasets. Our overall findings do not support a detectable association between the recent adaptive evolution of either ASPM or Microcephalin and changes in IQ. As we enter the post-genomic era, with the number of candidate loci underlying human evolution growing rapidly, our findings highlight the importance of direct experimental validation in elucidating their evolutionary role in shaping the human phenotype.
journal_name
Hum Mol Genetjournal_title
Human molecular geneticsauthors
Mekel-Bobrov N,Posthuma D,Gilbert SL,Lind P,Gosso MF,Luciano M,Harris SE,Bates TC,Polderman TJ,Whalley LJ,Fox H,Starr JM,Evans PD,Montgomery GW,Fernandes C,Heutink P,Martin NG,Boomsma DI,Deary IJ,Wright MJ,de Geusdoi
10.1093/hmg/ddl487subject
Has Abstractpub_date
2007-03-15 00:00:00pages
600-8issue
6eissn
0964-6906issn
1460-2083pii
ddl487journal_volume
16pub_type
杂志文章abstract::CDH3/P-cadherin is a classical cadherin. Overexpression of which has been associated with proliferative lesions of high histological grade, decreased cell polarity and poor survival of patients with breast cancer. In vitro studies showed that it can be up-regulated by ICI 182,780, suggesting that the lack of ERalpha s...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddq134
更新日期:2010-07-01 00:00:00
abstract::Despite the clinical importance of human aneuploidy, we know little of the causes of mammalian non-disjunction. In part, this reflects the fact that, unlike lower organisms, segregation 'impaired' chromosomes are virtually non-existent in mammals. To address this issue, we have studied the mouse Y chromosome on the BA...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/10.9.963
更新日期:2001-04-15 00:00:00
abstract::Huntington's disease is caused by an expanded polyglutamine tract in huntingtin protein, leading to accumulation of huntingtin in the nuclei of striatal neurons. The 18 amino-acid amino-terminus of huntingtin is an amphipathic alpha helical membrane-binding domain that can reversibly target to vesicles and the endopla...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddm217
更新日期:2007-11-01 00:00:00
abstract::Recent studies suggest that the genome is organized into blocks of haplotypes, and efforts to create a genome-wide haplotype map of single-nucleotide polymorphisms (SNPs) are already underway. Haplotype blocks are defined algorithmically and to date several algorithms have been proposed. However, little is known about...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddh035
更新日期:2004-02-01 00:00:00
abstract::Mutations in Fused in sarcoma (FUS) gene cause a subset of familial amyotrophic lateral sclerosis (ALS), a fatal motor neuron degenerative disease. Wild-type FUS is largely localized in the nucleus, but mutant FUS accumulates in the cytoplasm and forms inclusions. It is unclear whether FUS depletion from the nucleus o...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddv239
更新日期:2015-09-15 00:00:00
abstract::Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder caused by polyglutamine expansion in the disease protein, huntingtin. In HD patients and transgenic mice, the affected neurons form characteristic ubiquitin-positive nuclear inclusions (NIs). We have established ecdysone-inducible stable mou...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/9.13.2009
更新日期:2000-08-12 00:00:00
abstract::The recently described DNA replication-based mechanisms of fork stalling and template switching (FoSTeS) and microhomology-mediated break-induced replication (MMBIR) were previously shown to catalyze complex exonic, genic and genomic rearrangements. By analyzing a large number of isochromosomes of the long arm of chro...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddr074
更新日期:2011-05-15 00:00:00
abstract::Targeting of numerous transmembrane proteins to the cell surface is thought to depend on their recognition by cargo receptors that interact with the adaptor machinery for anterograde traffic at the distal end of the Golgi complex. We report here on consortin, a novel integral membrane protein that is predicted to be i...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddp490
更新日期:2010-01-15 00:00:00
abstract::We have constructed a long-range restriction map of the region on chromosome 4q that contains the gene for facioscapulohumeral muscular dystrophy (FSHD). This region contains the linkage group cen ... D4S163-D4S139-D4F35S1-D4F104S1-FSHD ... 4qter, which spans a genetic distance of about 5 cM. Pulse field gel electroph...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/2.10.1667
更新日期:1993-10-01 00:00:00
abstract::Congenital vertebral malformations (CVMs) are associated with human TBX6 compound inheritance that combines a rare null allele and a common hypomorphic allele at the TBX6 locus. Our previous in vitro evidence suggested that this compound inheritance resulted in a TBX6 gene dosage of less than haploinsufficiency (i.e. ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddy358
更新日期:2019-02-15 00:00:00
abstract::Spinal muscular atrophy (SMA), a frequent neurodegenerative disease, is caused by reduced levels of functional survival of motoneuron (SMN) protein. SMN is involved in multiple pathways, including RNA metabolism and splicing as well as motoneuron development and function. Here we provide evidence for a major contribut...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddr425
更新日期:2011-12-15 00:00:00
abstract::We introduced a targeted single base deletion at codon 307 of the rds-peripherin gene in mice, similar mutations being known to cause autosomal dominant retinitis pigmentosa (RP) in man. Histopathological and electroretinographic analysis indicate that the retinopathy in mice homozygous for the codon 307 mutation appe...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/11.9.1005
更新日期:2002-05-01 00:00:00
abstract::Osteoarthritis (OA) is a common, multifactorial and polygenic skeletal disease that, in its severest form, requires joint replacement surgery to restore mobility and to relieve chronic pain. Using tissues from the articulating joints of 260 patients with OA and a range of in vitro experiments, including CRISPR-Cas9, w...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddy257
更新日期:2018-10-01 00:00:00
abstract::Blood levels of adiponectin, an adipocyte-secreted protein correlated with metabolic and cardiovascular risks, are highly heritable. Genome-wide association (GWA) studies for adiponectin levels have identified 14 loci harboring variants associated with blood levels of adiponectin. To identify novel adiponectin-associa...
journal_title:Human molecular genetics
pub_type: 杂志文章,meta分析
doi:10.1093/hmg/ddt488
更新日期:2014-02-15 00:00:00
abstract::According to the telomere hypothesis of senescence, the progressive shortening of telomeres that occurs upon division of normal somatic cells eventually leads to cellular senescence. The immortalisation of human cells is associated with the acquisition of a telomere maintenance mechanism which is usually dependent upo...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/6.6.921
更新日期:1997-06-01 00:00:00
abstract::In mammals, sperm-oocyte fusion initiates Ca(2+) oscillations leading to a series of events called oocyte activation, which is the first stage of embryo development. Ca(2+) signaling is elicited by the delivery of an oocyte-activating factor by the sperm. A sperm-specific phospholipase C (PLCZ1) has emerged as the lik...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddv617
更新日期:2016-03-01 00:00:00
abstract::Subcortical band heterotopia (SBH) are bilateral and symmetric ribbons of gray matter found in the central white matter between the cortex and the ventricular surface, which comprises the less severe end of the lissencephaly (agyria-pachygyria-band) spectrum of malformations. Mutations in DCX (also known as XLIS ) hav...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/8.9.1757
更新日期:1999-09-01 00:00:00
abstract::Genetic polymorphisms are thought to play an important role in determining susceptibility to neural tube defects (NTDs), for example between different ethnic groups, but the embryonic manifestation of these polymorphic genetic influences is unclear. We have used a mouse model to test experimentally whether polymorphic...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/9.4.575
更新日期:2000-03-01 00:00:00
abstract::Determination of variant pathogenicity represents a major challenge in the era of high-throughput sequencing. Erroneous categorization may result if variants affect genes that are in fact dispensable. We demonstrate that this also applies to rare, apparently unambiguous truncating mutations of an established disease g...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddv022
更新日期:2015-05-01 00:00:00
abstract::Increased age, BMI and HbA1c levels are risk factors for several non-communicable diseases. However, the impact of these factors on the genome-wide DNA methylation pattern in human adipose tissue remains unknown. We analyzed the DNA methylation of ∼480 000 sites in human adipose tissue from 96 males and 94 females and...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddv124
更新日期:2015-07-01 00:00:00
abstract::Muscular dystrophies are a group of genetic diseases that lead to muscle wasting and, in most cases, premature death. Cytokines and inflammatory factors are released during the disease process where they promote deleterious signaling events that directly participate in myofiber death. Here, we show that p38α, a kinase...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddu270
更新日期:2014-10-15 00:00:00
abstract::Ubiquinone (UQ), a.k.a. coenzyme Q, is a redox-active lipid that participates in several cellular processes, in particular mitochondrial electron transport. Primary UQ deficiency is a rare but severely debilitating condition. Mclk1 (a.k.a. Coq7) encodes a conserved mitochondrial enzyme that is necessary for UQ biosynt...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddt330
更新日期:2013-12-01 00:00:00
abstract::Following a screen for neuromuscular mouse mutants, we identified ostes, a novel N-ethyl N-nitrosourea-induced mouse mutant with muscle atrophy. Genetic and biochemical evidence shows that upregulation of the novel, uncharacterized transient receptor potential polycystic (TRPP) channel PKD1L2 (polycystic kidney diseas...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddp304
更新日期:2009-10-01 00:00:00
abstract::Although genetic variations in several genes encoding for synaptic adhesion proteins have been found to be associated with autism spectrum disorders, one of the most consistently replicated genes has been CNTNAP2, encoding for contactin-associated protein-like 2 (CASPR2), a multidomain transmembrane protein of the neu...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/dds320
更新日期:2012-11-01 00:00:00
abstract::Migraine is a prevalent, debilitating and costly disorder with an ongoing unmet medical need. Human genetic studies have provided considerable insights into the molecular underpinnings of this complex brain disorder. Classical linkage studies have revealed the causes of familial hemiplegic migraine, while more recentl...
journal_title:Human molecular genetics
pub_type: 杂志文章,评审
doi:10.1093/hmg/ddt364
更新日期:2013-10-15 00:00:00
abstract::γ-secretase is a macromolecular complex that catalyzes intramembranous hydrolysis of more than 100 membrane-bound substrates. The complex is composed of presenilin (PS1 or PS2), anterior pharynx defect-1 (APH-1), nicastrin (NCT) and PEN-2 and early-onset; autosomal dominant forms of Alzheimer's disease (AD) are caused...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddaa017
更新日期:2020-04-15 00:00:00
abstract::Nemaline myopathy (NM), the most common non-dystrophic congenital myopathy, is a variably severe neuromuscular disorder for which no effective treatment is available. Although a number of genes have been identified in which mutations can cause NM, the pathogenetic mechanisms leading to the phenotypes are poorly unders...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddl186
更新日期:2006-09-01 00:00:00
abstract::The early growth response 2 gene ( EGR2 ) is a Cys2His2zinc finger transcription factor which is thought to play a role in the regulation of peripheral nervous system myelination. This idea is based partly on the phenotype of homozygous Krox20 ( Egr2 ) knockout mice, which display hypomyelination of the PNS and a bloc...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/8.7.1245
更新日期:1999-07-01 00:00:00
abstract::Several human inherited diseases have been localized to the Xq13.3 region of the human X chromosome (X-linked dystonia with Parkinsonism, sideroblastic anemia, SCID, Menkes disease and X-linked mental retardation loci). Genes involved in the phenotypes have been isolated for only two of them (Menkes and SCIDX). It was...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/3.1.39
更新日期:1994-01-01 00:00:00
abstract::A transcription map of the Huntington disease gene region was generated by a direct cDNA selection strategy using genomic DNA from the 4p16.3 region surrounding the D4S95 and D4S127 loci. A total of 58 cDNA fragments were obtained from cDNAs derived from fetal brain, frontal cortex, liver and bone marrow following hyb...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/2.7.901
更新日期:1993-07-01 00:00:00