Abstract：
:Studies in mouse and chick have shown that the 5' HoxD genes play major roles in the development of the limbs and genitalia. In humans, mutations in HOXD13 cause the dominantly inherited limb malformation synpolydactyly (SPD). Haploinsufficiency for the 5' HOXD genes has recently been proposed to underlie the monodactyly and penoscrotal hypoplasia in two children with chromosomal deletions encompassing the entire HOXD cluster. Similar deletions, however, have previously been associated with split-hand/foot malformation (SHFM), including monodactyly. Here we report a father and daughter with SPD who carry a 117-kb microdeletion at the 5' end of the HOXD cluster. By sequencing directly across the deletion breakpoint, we show that this microdeletion removes only HOXD9-HOXD13 and EVX2. We also report a girl with bilateral split foot and a chromosomal deletion that includes the entire HOXD cluster and extends approximately 5 Mb centromeric to it. Our findings indicate that haploinsufficiency for the 5' HOXD genes causes not SHFM but SPD and point to the presence of a novel locus for SHFM in the interval between EVX2 and D2S294. They also suggest that there is a regulatory region, upstream of the HOXD cluster, that is responsible for activating the cluster as a whole.
journal_name
Am J Hum Genetjournal_title
American journal of human geneticsauthors
Goodman FR,Majewski F,Collins AL,Scambler PJdoi
10.1086/338921subject
Has Abstractpub_date
2002-02-01 00:00:00pages
547-55issue
2eissn
0002-9297issn
1537-6605pii
S0002-9297(07)63969-Xjournal_volume
70pub_type
杂志文章abstract：:The elucidation of the largely unknown transcriptome of small RNAs is crucial for the understanding of genome and cellular function. We report here the results of the analysis of small RNAs (< 50 nt) in the ENCODE regions of the human genome. Size-fractionated RNAs from four different cell lines (HepG2, HelaS3, GM0699...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2008.02.016
更新日期：2008-04-01 00:00:00
abstract：:In spondylocostal dysostosis (SD), vertebral-segmentation defects are associated with rib anomalies. This results in short-trunk short stature, nonprogressive kyphoscoliosis, and radiological features of multiple hemivertebrae and rib fusions. SD can be familial, and both autosomal dominant and autosomal recessive (AR...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/302464
更新日期：1999-07-01 00:00:00
abstract：:Early B cell factor 3 (EBF3) is an atypical transcription factor that is thought to influence the laminar formation of the cerebral cortex. Here, we report that de novo mutations in EBF3 cause a complex neurodevelopmental syndrome. The mutations were identified in two large-scale sequencing projects: the UK Decipherin...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2016.11.020
更新日期：2017-01-05 00:00:00
abstract：:The extent to which variants in the protein-coding sequence of genes contribute to risk of rheumatoid arthritis (RA) is unknown. In this study, we addressed this issue by deep exon sequencing and large-scale genotyping of 25 biological candidate genes located within RA risk loci discovered by genome-wide association s...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2012.11.012
更新日期：2013-01-10 00:00:00
abstract：:Height has been used for more than a century as a model by which to understand quantitative genetic variation in humans. We report that the entire genome appears to contribute to its additive genetic variance. We used genotypes and phenotypes of 11,214 sibling pairs from three countries to partition additive genetic v...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/522934
更新日期：2007-11-01 00:00:00
abstract：:Hereditary multiple exostoses (EXT) is an autosomal dominant disorder characterized by the formation of cartilage-capped prominences that develop from the growth centers of the long bones. EXT is genetically heterogeneous, with three loci, currently identified on chromosomes 8q24.1, 11p13, and 19q. The EXT1 gene, loca...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1997-01-01 00:00:00
abstract：:Spinal Muscular Atrophy (SMA) is an inherited degenerative disorder of anterior horn cells that results in progressive muscle weakness and atrophy. The autosomal recessive forms of childhood-onset SMA have been mapped to chromosome 5q11.2-13.3, in a number of studies examining different populations. A total of 9 simpl...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1995-01-01 00:00:00
abstract：:Epigenetic modifications such as DNA methylation play a key role in gene regulation and disease susceptibility. However, little is known about the genome-wide frequency, localization, and function of methylation variation and how it is regulated by genetic and environmental factors. We utilized the Multiple Tissue Hum...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2013.10.004
更新日期：2013-11-07 00:00:00
abstract：:Retinitis pigmentosa is the name given to a heterogeneous group of hereditary retinal degenerations characterized by progressive visual field loss, pigmentary changes of the retina, abnormal electroretinograms, and, frequently, night blindness. In this study, we investigated a family with dominant cone-rod degeneratio...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1995-07-01 00:00:00
abstract：:Although recent studies provide evidence for a common genetic basis between complex traits and Mendelian disorders, a thorough quantification of their overlap in a phenotype-specific manner remains elusive. Here, we have quantified the overlap of genes identified through large-scale genome-wide association studies (GW...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2018.08.017
更新日期：2018-10-04 00:00:00
abstract：:Sensorineural deafness and retinitis pigmentosa (RP) are the hallmarks of Usher syndrome (USH) but are also prominent features in peroxisomal biogenesis defects (PBDs); both are autosomal recessively inherited. The firstborn son of unrelated parents, who both had sensorineural deafness and RP diagnosed as USH, present...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/339766
更新日期：2002-04-01 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：:The fourth-year medical student elective in clinical genetics has been enhanced by the addition of a problem-solving project. The assignment requires students to pose and answer a practical question about a professionally relevant genetic problem. Exemplary questions and the details of the exercise are given. Six of 1...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1991-08-01 00:00:00
abstract：:Protoporphyria is an autosomal dominant disease in man in which protoporphyrin accumulated because of a defect in heme synthase (ferrochelatase) activity. A disease has been described in cattle that has the same manifestations as does the human disease. We measured heme synthase activity in sonicates of cultured skin ...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1982-03-01 00:00:00
abstract：:A convenient and reliable method for simulatneous visualization of silver staining (Ag-NOR) of the nucleolus organizers and fluorescent bandings in metaphase chromosomes is described. Studies employing this combined procedure on human chromosomes revealed that the Ag-NOR patterns may be characteristic for each chromos...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1978-01-01 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：:The purpose of this study was to characterize the mutant enzyme in nine patients with gyrate atrophy of the choroid and retina associated with ornithine aminotransferase (OAT) deficiency, to elucidate the mechanism of response to pyridoxine in four pyridoxine-responsive patients, and to determine the extent of genetic...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1989-03-01 00:00:00
abstract：:We determined the mutation spectrum of the RP2 and RPGR genes in patients with X-linked retinitis pigmentosa (XLRP) and searched for correlations between categories of mutation and severity of disease. We screened 187 unrelated male patients for mutations, including 135 with a prior clinical diagnosis of XLRP, 11 with...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/379379
更新日期：2003-11-01 00:00:00
abstract：:In this report, we describe a simple correction for multiple testing of single-nucleotide polymorphisms (SNPs) in linkage disequilibrium (LD) with each other, on the basis of the spectral decomposition (SpD) of matrices of pairwise LD between SNPs. This method provides a useful alternative to more computationally inte...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/383251
更新日期：2004-04-01 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：:Although psoriasis is strongly associated with certain human leukocyte antigens (HLAs), evidence for linkage to HLA markers has been limited. The objectives of this study were (1) to provide more definitive evidence for linkage of psoriasis to HLA markers in multiplex families; (2) to compare the major HLA risk allele...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/301899
更新日期：1998-07-01 00:00:00
abstract：:When the mode of inheritance of a disease is unknown, the LOD-score method of linkage analysis must take into account uncertainties in model parameters. We have previously proposed a parametric linkage test called "MFLOD," which does not require specification of disease model parameters. In the present study, we intro...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/302888
更新日期：2000-05-01 00:00:00
abstract：:Myotonic dystrophy (DM) is a progressive neuromuscular disorder which results from elongations of an unstable (CTG)n repeat, located in the 3' untranslated region of the DM gene. A correlation has been demonstrated between the increase in the repeat number of this sequence and the severity of the disease. However, the...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1993-05-01 00:00:00
abstract：:The Million Veteran Program (MVP), initiated by the Department of Veterans Affairs (VA), aims to collect biosamples with consent from at least one million veterans. Presently, blood samples have been collected from over 800,000 enrolled participants. The size and diversity of the MVP cohort, as well as the availabilit...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2020.03.004
更新日期：2020-04-02 00:00:00
abstract：:Cellular DNAs from a panel of 20 unrelated individuals were screened for restriction fragment length polymorphisms (RFLP) with a DNA probe containing the first exon of the proopiomelanocortin gene (POMC), which has been assigned to chromosome 2p23-25. Digestion with the restriction endonuclease Sst 1 revealed a high f...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1983-11-01 00:00:00
abstract：:The allele frequency distribution of two highly polymorphic DNA sequences has been determined in three ethnic groups (American blacks, Caucasoids, and Hispanics) from the New York metropolitan area. The two loci examined were D14S1 and the flanking region of HRAS-1. The former was analyzed in EcoRI-digested DNA and th...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1986-10-01 00:00:00
abstract：:The alkaline phosphatases comprise a multigene enzyme family that hydolyze phosphate esters and are widely distributed in nature. Three main classes have been isolated from humans, the placental, intestinal, and liver/bone/kidney forms. We have mapped the placental and intestinal alkaline phosphatase genes to 2q34-q37...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1987-12-01 00:00:00
abstract：:Cigarette smoke, containing reactive oxygen species, is the most important risk factor for chronic pulmonary emphysema (CPE). Heme oxygenase-1 (HO-1) plays a protective role as an antioxidant in the lung. A (GT)n dinucleotide repeat in the 5'-flanking region of human HO-1 gene shows length polymorphism and could modul...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/302729
更新日期：2000-01-01 00:00:00
abstract：:Despite a significant genetic contribution to alcohol dependence (AD), few AD-risk genes have been identified to date. In the current study, we aimed to integrate genome-wide association studies (GWASs) and human protein interaction networks to investigate whether a subnetwork of genes whose protein products interact ...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2013.10.021
更新日期：2013-12-05 00:00:00
abstract：:Autosomal dominant progressive external ophthalmoplegia (adPEO) is a disorder characterized by ptosis, progressive weakness of the external eye muscles, and general muscle weakness. The patients have multiple deletions of mtDNA on Southern blots or in PCR analysis of muscle DNA and a mild deficiency of one or more res...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1996-04-01 00:00:00
