Abstract：
:Although Africa has played a central role in human evolutionary history, certain studies have suggested that not all contemporary human genetic diversity is of recent African origin. We investigated 35 simple polymorphic sites and one T(n) microsatellite in an 8-kb segment of the dystrophin gene. We found 86 haplotypes in 1,343 chromosomes from around the world. Although a classical out-of-Africa topology was observed in trees based on the variant frequencies, the tree of haplotype sequences reveals three lineages accounting for present-day diversity. The proportion of new recombinants and the diversity of the T(n) microsatellite were used to estimate the age of haplotype lineages and the time of colonization events. The lineage that underwent the great expansion originated in Africa prior to the Upper Paleolithic (27,000-56,000 years ago). A second group, of structurally distinct haplotypes that occupy a central position on the tree, has never left Africa. The third lineage is represented by the haplotype that lies closest to the root, is virtually absent in Africa, and appears older than the recent out-of-Africa expansion. We propose that this lineage could have left Africa before the expansion (as early as 160,000 years ago) and admixed, outside of Africa, with the expanding lineage. Contemporary human diversity, although dominated by the recently expanded African lineage, thus represents a mosaic of different contributions.
journal_name
Am J Hum Genetjournal_title
American journal of human geneticsauthors
Zietkiewicz E,Yotova V,Gehl D,Wambach T,Arrieta I,Batzer M,Cole DE,Hechtman P,Kaplan F,Modiano D,Moisan JP,Michalski R,Labuda Ddoi
10.1086/378777subject
Has Abstractpub_date
2003-11-01 00:00:00pages
994-1015issue
5eissn
0002-9297issn
1537-6605pii
S0002-9297(07)61964-8journal_volume
73pub_type
杂志文章abstract：:The cloning of the CFTR gene has made it technically possible to avert the unwanted birth of a child with cystic fibrosis (CF). Several large trials offering prenatal CF carrier screening suggest that such screening is practical and that identified carriers generally use the information obtained. Therefore, a critical...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/302042
更新日期：1998-10-01 00:00:00
abstract：:The first component of the mitochondrial electron-transport chain is especially complex, consisting of 19 nuclear and seven mitochondrion-encoded subunits. Accordingly, a wide range of clinical manifestations are produced by the various mutations occurring in human populations. In this study, we analyze the subunit st...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1991-06-01 00:00:00
abstract：:Chromosomal aneuploidy is usually identified by cytogenetic methods. However, for some purposes it would be desirable to have an easier method of recognizing specific trisomies or monosomies. We have devised such an assay. It involves the simultaneous hybridization of two chromosome-specific DNA probes labeled with di...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1988-10-01 00:00:00
abstract：:Multiple morphological abnormalities of the sperm flagellum (MMAF) is a severe form of male infertility defined by the presence of a mosaic of anomalies, including short, bent, curled, thick, or absent flagella, resulting from a severe disorganization of the axoneme and of the peri-axonemal structures. Mutations in DN...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2018.07.014
更新日期：2018-09-06 00:00:00
abstract：:A nonparametric statistical methodology is used for the analysis of biochemical frequency data observed on a series of nine Jewish and six non-Jewish populations. Two categories of statistics are used: heterogeneity indices and various distance measures with respect to a standard. The latter are more discriminating in...
journal_title：American journal of human genetics
pub_type： 历史文章,杂志文章
doi：
更新日期：1979-05-01 00:00:00
abstract：:Gilles de la Tourette syndrome is a neuropsychiatric disorder characterized by waxing and waning multiple motor and phonic tics with a complex mode of inheritance. Previous attempts, which used large multigenerational families to localize susceptibility loci, have been unsuccessful. In this report, the results of the ...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/302613
更新日期：1999-11-01 00:00:00
abstract：:Galactosemia is an autosomal recessive disorder of human galactose metabolism caused by deficiency of the enzyme galactose-1-phosphate uridyl transferase (GALT). The molecular basis of this disorder is at present not well understood. We report here two missense mutations which result in low or undetectable enzymatic a...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1991-10-01 00:00:00
abstract：:To detect heterozygotes for maple-syrup-urine disease (MSUD), activities of branched-chain-alpha-ketoacid (BCKA) dehydrogenase and its components in skin fibroblasts of two obligatory heterozygotes and amnion cells of a fetus at risk were measured. Intact heterozygous cells were found to decarboxylate [1-14C] alpha-ke...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1982-05-01 00:00:00
abstract：:Previously, we demonstrated evidence of linkage to bipolar affective disorder (BP) in a single large, multigenerational family with a LOD score of 3.41 at the PFKL locus on chromosome 21q22.3. Additional families showed little support for linkage to PFKL under homogeneity or heterogeneity, in that study. We have expan...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/302185
更新日期：1999-01-01 00:00:00
abstract：:Arthrogryposis is a clinical finding that is present either as a feature of a neuromuscular condition or as part of a systemic disease in over 400 Mendelian conditions. The underlying molecular etiology remains largely unknown because of genetic and phenotypic heterogeneity. We applied exome sequencing (ES) in a cohor...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2019.05.015
更新日期：2019-07-03 00:00:00
abstract：:The tRNA synthetases catalyze the first step of protein synthesis and have increasingly been studied for their nuclear and extra-cellular ex-translational activities. Human genetic conditions such as Charcot-Marie-Tooth have been attributed to dominant gain-of-function mutations in some tRNA synthetases. Unlike domina...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2018.06.006
更新日期：2018-07-05 00:00:00
abstract：:Molecular linkage analysis was performed on a kindred with X-linked sideroblastic anemia and ataxia. Two-point analysis with a DNA probe for phosphoglycerate kinase (PGK1), which maps to Xq13, suggested linkage to the disorder by a lod score of at least 2.60 at a recombination fraction of zero. The disease in this kin...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1991-02-01 00:00:00
abstract：:Although balanced translocations are among the most common human chromosomal aberrations, the constitutional t(11;22)(q23;q11) is the only known recurrent non-Robertsonian translocation. Evidence indicates that de novo formation of the t(11;22) occurs during meiosis. To test the hypothesis that spatial proximity of ch...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/507652
更新日期：2006-09-01 00:00:00
abstract：:Isolated complex I deficiency is a common biochemical phenotype observed in pediatric mitochondrial disease and often arises as a consequence of pathogenic variants affecting one of the ∼65 genes encoding the complex I structural subunits or assembly factors. Such genetic heterogeneity means that application of next-g...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2018.08.013
更新日期：2018-10-04 00:00:00
abstract：:Linkage analysis of phenylketonurics has shown a strong association between the DNA haplotype at the phenylalanine hydroxylase (PAH) locus and phenylketonuria (PKU). Similarly, a genetic linkage between less severe forms of hyperphenylalaninemia (HPA) and the PAH locus has been suggested. In the present study we analy...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1990-10-01 00:00:00
abstract：:The parental origin of the supernumerary chromosome 18 was investigated by RFLP analysis in 23 individuals with Edwards syndrome. All families were studied with the DNA probe pERT-25, which recognizes a locus of highly polymorphic tandemly repeated DNA sequences on chromosome 18. The extra chromosome was found to be o...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1989-10-01 00:00:00
abstract：:Spinal muscular atrophy (SMA) is a clinically and genetically heterogeneous disease characterized by the degeneration of lower motor neurons. The most frequent form is linked to mutations in SMN1. Childhood SMA associated with progressive myoclonic epilepsy (SMA-PME) has been reported as a rare autosomal-recessive con...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2012.05.001
更新日期：2012-07-13 00:00:00
abstract：:Steroid-resistant nephrotic syndrome (SRNS) is characterized by high-range proteinuria and most often focal and segmental glomerulosclerosis (FSGS). Identification of mutations in genes causing SRNS has improved our understanding of disease mechanisms and highlighted defects in the podocyte, a highly specialized glome...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2018.12.016
更新日期：2019-02-07 00:00:00
abstract：:Recombination rates vary both across the genome and between different species, but little information is available about the temporal and physical scales over which such rates change. To shed light on these questions, we performed a high-resolution analysis of a genomic region within the beta-globin gene cluster that ...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/380311
更新日期：2003-12-01 00:00:00
abstract：:In this report we describe the use of dystrophin analysis both in the diagnosis of Duchenne muscular dystrophy (DMD) in an aborted fetus and in genetic counseling. Our consultand's initial carrier risk, as based on family history and creatine kinase determinations, was calculated as 0.6%. DNA analysis of her family (a...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1989-09-01 00:00:00
abstract：:A study was undertaken to characterize the mutation(s) responsible for Tay-Sachs disease (TSD) in a Cajun population in southwest Louisiana and to identify the origins of these mutations. Eleven of 12 infantile TSD alleles examined in six families had the beta-hexosaminidase A (Hex A) alpha-subunit exon 11 insertion m...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1992-11-01 00:00:00
abstract：:A linkage analysis is reported for three branches of a single family segregating for autosomal dominant retinitis pigmentosa. A statistically significant lod score of 3.9 is obtained for the RP locus and AMY2 at a recombination frequency of 1%. This linkage indicates that the RP locus is on the no. 1 chromosome since ...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1977-07-01 00:00:00
abstract：:The identification of pathways that underlie common disease has been greatly impacted by the study of rare families that segregate single genes with large effect. Intracranial aneurysm is a common neurological problem; the rupture of these aneurysms constitutes a frequently catastrophic neurologic event. The pathogene...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/426953
更新日期：2005-01-01 00:00:00
abstract：:Achieving long-term expression of a therapeutic gene in a given hematopoietic lineage remains an important goal of gene therapy. Congenital erythropoietic porphyria (CEP) is a severe autosomal-recessive disorder characterized by a deficiency in uroporphyrinogen III synthase (UROS), the fourth enzyme of the heme biosyn...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2007.09.007
更新日期：2008-01-01 00:00:00
abstract：:Van der Woude syndrome (VWS) is an autosomal dominant disorder in which affected individuals have one or more of the following manifestations: cleft lip, cleft palate, hypodontia, or paramedian lower-lip pits. VWS is a well-characterized example of a single-gene abnormality that disturbs normal craniofacial morphogene...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1990-03-01 00:00:00
abstract：:We report the development and validation of experimental methods, study designs, and analysis software for pooling-based genomewide association (GWA) studies that use high-throughput single-nucleotide-polymorphism (SNP) genotyping microarrays. We first describe a theoretical framework for establishing the effectivenes...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/510686
更新日期：2007-01-01 00:00:00
abstract：:The results of an empirical nucleotide-sequencing approach indicate that the evolution of the human mitochondrial noncoding D-loop is both more rapid and more complex than is revealed by standard phylogenetic approaches. The nucleotide sequence of the D-loop region of the mitochondrial genome was determined for 45 mem...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1996-09-01 00:00:00
abstract：:Beta-Glucosidase activity measured by synthetic substrate at pH 4.6 was low in the cultured amniotic cells from two pregnant women at risk for juvenile and adult type Gaucher disease. The diagnosis was confirmed by showing a low activity of beta-glucosidase in the skin fibroblasts with a synthetic substrate or in the ...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1978-05-01 00:00:00
abstract：:Patients with dyskeratosis congenita (DC), a heterogeneous inherited bone marrow failure syndrome, have abnormalities in telomere biology, including very short telomeres and germline mutations in DKC1, TERC, TERT, or NOP10, but approximately 60% of DC patients lack an identifiable mutation. With the very short telomer...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2007.10.004
更新日期：2008-02-01 00:00:00
abstract：:Lissencephaly is a malformation of cortical development typically caused by deficient neuronal migration resulting in cortical thickening and reduced gyration. Here we describe a "thin" lissencephaly (TLIS) variant characterized by megalencephaly, frontal predominant pachygyria, intellectual disability, and seizures. ...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2016.09.010
更新日期：2016-11-03 00:00:00
