Abstract:
:Admixture mapping requires a genomewide panel of relatively evenly spaced markers that can distinguish the ancestral origins of chromosomal segments in admixed individuals. Through use of the results of the International HapMap Project and specific selection criteria, the current study has examined the ability of selected single-nucleotide polymorphisms (SNPs) to extract continental ancestry information in African American subjects and to explore parameters for admixture mapping. Genotyping of two linguistically diverse West African populations (Bini and Kanuri Nigerians, who are Niger-Congo [Bantu] and Nilo-Saharan speakers, respectively), European Americans, and African Americans validated a genomewide set of >4,000 SNP ancestry-informative markers with mean and median F(ST) values >0.59 and mean and median Fisher's information content >2.5. This set of SNPs extracted a larger amount of ancestry information in African Americans than previously reported SNP panels and provides nearly uniform coverage of the genome. Moreover, in the current study, simulations show that this more informative panel improves power for admixture mapping in African Americans when ethnicity risk ratios are modest. This is particularly important in the application of admixture mapping in complex genetic diseases for which only modest ethnicity risk ratios of relevant susceptibility genes are expected.
journal_name
Am J Hum Genetjournal_title
American journal of human geneticsauthors
Tian C,Hinds DA,Shigeta R,Kittles R,Ballinger DG,Seldin MFdoi
10.1086/507954subject
Has Abstractpub_date
2006-10-01 00:00:00pages
640-9issue
4eissn
0002-9297issn
1537-6605pii
S0002-9297(07)63074-2journal_volume
79pub_type
杂志文章abstract::We identified four different missense mutations in the single-exon gene MAB21L2 in eight individuals with bilateral eye malformations from five unrelated families via three independent exome sequencing projects. Three mutational events altered the same amino acid (Arg51), and two were identical de novo mutations (c.15...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2014.05.005
更新日期:2014-06-05 00:00:00
abstract::Hirschsprung disease (HSCR) is a common congenital disorder characterized by aganglionosis of the gut. The seemingly unrelated multiple endocrine neoplasia type 2 (MEN 2) is an autosomal dominant disorder characterized by medullary thyroid carcinoma (MTC), pheochromocytoma, and hyperparathyroidism. Yet, germline mutat...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/345466
更新日期:2003-01-01 00:00:00
abstract::A genetic approach is used to ascertain that a single structural locus for triosephosphate isomerase (TPI) (E.C.5.3.1.1.) is expressed in rapidly dividing human lymphoblasts. This approach is made possible through the identification of a rare electrophoretic variant of human TPI. The variant phenotype is expressed by ...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1981-09-01 00:00:00
abstract::Comparisons are presented of the ages of onset of 20 cases of hereditary medullary carcinoma of the thyroid (MCT) and of 22 sporadic cases of this same type of cancer. These data are compatible with what might be expected by the two-mutational-event theory of the initiation of cancer postulated by Knudson. It had been...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1979-11-01 00:00:00
abstract::The identification of genes associated with hereditary disorders has contributed to improving medical care and to a better understanding of gene functions, interactions, and pathways. However, there are well over 1500 Mendelian disorders whose molecular basis remains unknown. At present, methods such as linkage analys...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2008.02.013
更新日期:2008-04-01 00:00:00
abstract::Tyrosinase-positive oculocutaneous albinism (ty-pos OCA) is an autosomal recessive disorder of the melanin pigmentary system. South African ty-pos OCA individuals occur with two distinct phenotypes, with or without darkly pigmented patches (ephelides, or dendritic freckles) on exposed areas of the skin. These phenotyp...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1994-06-01 00:00:00
abstract::Renal stone formation is a common multifactorial disorder, of unknown etiology, with an established genetic contribution. Lifetime risk for nephrolithiasis is approximately 10% in Western populations, and uric acid stones account for 5%-10% of all stones, depending on climatic, dietary, and ethnic differences. We stud...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/320105
更新日期:2001-05-01 00:00:00
abstract::Human fetuses with trisomy 21 (T21) have atypical brain development that is apparent sonographically in the second trimester. We hypothesize that by analyzing and integrating dysregulated gene expression and pathways common to humans with Down syndrome (DS) and mouse models we can discover novel targets for prenatal t...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2020.10.001
更新日期:2020-11-05 00:00:00
abstract::Synaptophysin is an integral membrane protein of small synaptic vesicles in brain and endocrine cells. We have determined the structure and organization of the human synaptophysin gene and have established the chromosome localizations in man and mouse. Analysis of a cosmid clone containing the human synaptophysin gene...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1990-09-01 00:00:00
abstract::The exploration of copy-number variation (CNV), notably of somatic cells, is an understudied aspect of genome biology. Any differences in the genetic makeup between twins derived from the same zygote represent an irrefutable example of somatic mosaicism. We studied 19 pairs of monozygotic twins with either concordant ...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2007.12.011
更新日期:2008-03-01 00:00:00
abstract::To provide a definitive linkage map for multiple sclerosis, we have genotyped the Illumina BeadArray linkage mapping panel (version 4) in a data set of 730 multiplex families of Northern European descent. After the application of stringent quality thresholds, data from 4,506 markers in 2,692 individuals were included ...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/444547
更新日期:2005-09-01 00:00:00
abstract::Four subjects with thermolabile methylenetetrahydrofolate reductase (MTHFR) were discovered among 16 "obligate" heterozygotes for severe MTHFR deficiency and their family members. All four subjects had less than 25% of normal mean MTHFR specific activity in lymphocyte extracts. Three of them with normal serum folate a...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1991-03-01 00:00:00
abstract::The homodimeric transmembrane receptor natriuretic peptide receptor B (NPR-B [also known as guanylate cyclase B, GC-B, and GUC2B]; gene name NPR2) produces cytoplasmic cyclic GMP from GTP on binding its extracellular ligand, C-type natriuretic peptide (CNP). CNP has previously been implicated in the regulation of skel...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/422013
更新日期:2004-07-01 00:00:00
abstract::In the present report, we summarize studies aimed at examining the reliability of chromosome heteromorphisms in analyses of chromosome 21 nondisjunction. We used two cytogenetic approaches--fluorescent in situ hybridization (FISH) to repetitive sequences on 21p and traditional Q-banding--to distinguish chromosome 21 h...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1992-12-01 00:00:00
abstract::Ataxia-pancytopenia (AP) syndrome is characterized by cerebellar ataxia, variable hematologic cytopenias, and predisposition to marrow failure and myeloid leukemia, sometimes associated with monosomy 7. Here, in the four-generation family UW-AP, linkage analysis revealed four regions that provided the maximal LOD scor...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2016.04.009
更新日期:2016-06-02 00:00:00
abstract::The problem considered is that of estimating the age or rate of increase of a variant on the basis of the present number of replicates observed in a population. In place of previous diffusion equation analyses of age probability distributions, the likelihood for the age is studied on the basis of a discrete branching ...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1976-09-01 00:00:00
abstract::To establish the contribution of germline BRCA1 and BRCA2 mutations to familial ovarian cancer, we have analyzed both genes in DNA samples obtained from an affected individual in each of 112 families containing at least two cases of epithelial ovarian cancer. Germline mutations were found in 43% of the families; BRCA1...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/302583
更新日期:1999-10-01 00:00:00
abstract::Using sequence-tagged sites we have performed deletion mapping of the Y chromosome in sex-reversed female patients with a Y chromosome and gonadoblastoma. The GBY gene (gonadoblastoma locus on the Y chromosome) was sublocalized to a small region near the centromere of the Y chromosome. We estimate the size of the GBY ...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1995-12-01 00:00:00
abstract::A case of a 46,XYp- phenotypic female provided an opportunity to evaluate both sexual and somatic determinants for the Y chromosome. The patient had multiple stigmata of Turner syndrome, but normal stature. Laparotomy revealed a normal uterus and tubes, with 1.5 cm undifferentiated gonads. Serological tests for H-Y an...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1979-07-01 00:00:00
abstract::An autosomal recessive deficiency of acid alpha-glucosidase (GAA), type II glycogenosis, is genetically and clinically heterogeneous. The discovery of an enzyme-inactivating genomic deletion of exon 18 in three unrelated genetic compound patients--two infants and an adult--provided a rare opportunity to analyze the ef...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1995-04-01 00:00:00
abstract::Whole-genome and exome sequence data can be cost-effectively generated for the detection of rare-variant (RV) associations in families. Causal variants that aggregate in families usually have larger effect sizes than those found in sporadic cases, so family-based designs can be a more powerful approach than population...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2016.12.001
更新日期:2017-02-02 00:00:00
abstract::The debrisoquine/sparteine polymorphism is associated with a clinically important genetic deficiency of oxidative drug metabolism. From 5% to 10% of Caucasians designated as poor metabolizers (PMs) of the debrisoquine/sparteine polymorphism have a severely impaired capacity to metabolize more than 25 therapeutically u...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1991-05-01 00:00:00
abstract::One of the human urinary ribonucleases (RNases) was isolated and purified to homogeneity (SDS-PAGE) by means of a series of column chromatographies. The enzyme, designated RNase 1, is a glycoprotein with a molecular weight of approximately 16,000. Rabbit antibody to the purified RNase 1 reacted with human urine and se...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1988-04-01 00:00:00
abstract::Waardenburg anophthalmia syndrome, also known as microphthalmia with limb anomalies, ophthalmoacromelic syndrome, and anophthalmia-syndactyly, is a rare autosomal-recessive developmental disorder that has been mapped to 10p11.23. Here we show that this disease is heterogeneous by reporting on a consanguineous family, ...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2010.12.002
更新日期:2011-01-07 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::Carpenter syndrome is an autosomal-recessive multiple-congenital-malformation disorder characterized by multisuture craniosynostosis and polysyndactyly of the hands and feet; many other clinical features occur, and the most frequent include obesity, umbilical hernia, cryptorchidism, and congenital heart disease. Mutat...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2012.08.027
更新日期:2012-11-02 00:00:00
abstract::Restriction-fragment-length-polymorphism analysis was used to examine a female who is segregating for Duchenne muscular dystrophy (DMD) and a deletion of the DXS164 region of the X chromosome. The segregating female has no prior family history of DMD, and she has two copies of the DXS164 region in her peripheral blood...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1987-08-01 00:00:00
abstract::Hypotrichosis simplex (HS) comprises a group of hereditary isolated alopecias that are characterized by a diffuse and progressive loss of hair starting in childhood and shows a wide phenotypic variability. We mapped an autosomal-dominant form of HS to chromosome 1q31.3-1q41 in a Spanish family. By direct sequencing, w...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2012.10.022
更新日期:2013-01-10 00:00:00
abstract::We present the findings of a large linkage study of bipolar affective disorder (BPAD) that involved genomewide analysis of 52 families (448 genotyped individuals) of Spanish, Romany, and Bulgarian descent and further fine mapping of the 1p34-p36, 4q28-q31, and 6q15-q24 regions. An additional sample of 56 German famili...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/498619
更新日期:2005-12-01 00:00:00
abstract::The design and feasibility of whole-genome-association studies are critically dependent on the extent of linkage disequilibrium (LD) between markers. Although there has been extensive theoretical discussion of this, few empirical data exist. The authors have determined the extent of LD among 38 biallelic markers with ...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/316906
更新日期:2000-12-01 00:00:00