Abstract：
:Genetic mutations responsible for oblique facial clefts (ObFC), a unique class of facial malformations, are largely unknown. We show that loss-of-function mutations in SPECC1L are pathogenic for this human developmental disorder and that SPECC1L is a critical organizer of vertebrate facial morphogenesis. During murine embryogenesis, Specc1l is expressed in cell populations of the developing facial primordial, which proliferate and fuse to form the face. In zebrafish, knockdown of a SPECC1L homolog produces a faceless phenotype with loss of jaw and facial structures, and knockdown in Drosophila phenocopies mutants in the integrin signaling pathway that exhibit cell-migration and -adhesion defects. Furthermore, in mammalian cells, SPECC1L colocalizes with both tubulin and actin, and its deficiency results in defective actin-cytoskeleton reorganization, as well as abnormal cell adhesion and migration. Collectively, these data demonstrate that SPECC1L functions in actin-cytoskeleton reorganization and is required for proper facial morphogenesis.
journal_name
Am J Hum Genetjournal_title
American journal of human geneticsauthors
Saadi I,Alkuraya FS,Gisselbrecht SS,Goessling W,Cavallesco R,Turbe-Doan A,Petrin AL,Harris J,Siddiqui U,Grix AW Jr,Hove HD,Leboulch P,Glover TW,Morton CC,Richieri-Costa A,Murray JC,Erickson RP,Maas RLdoi
10.1016/j.ajhg.2011.05.023subject
Has Abstractpub_date
2011-07-15 00:00:00pages
44-55issue
1eissn
0002-9297issn
1537-6605pii
S0002-9297(11)00216-3journal_volume
89pub_type
杂志文章abstract：:In healthy individuals, fumarylacetoacetase (FAH) activities close to the range found in hereditary tyrosinemia type 1 (HT1) patients indicated the existence of a "pseudodeficiency" allele. In an individual homozygous for pseudodeficiency of FAH and in three HT1 families also carrying the pseudodeficiency allele, west...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1994-12-01 00:00:00
abstract：:Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are distinct neurobehavioral disorders that most often arise from a 4-Mb deletion of chromosome 15q11-q13 during paternal or maternal gametogenesis, respectively. At a de novo frequency of approximately.67-1/10,000 births, these deletions represent a common struct...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/302510
更新日期：1999-08-01 00:00:00
abstract：:An analysis of the inherited pattern of C-band heterochromatin has been made in five pedigrees containing a total of 33 offspring that were available for analysis. The majority of variants were found to be inherited; however, at least seven of the 99 variants were not present in either parent, and an additional seven ...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1975-03-01 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：:Carotid intimal medial thickness (IMT) is a heritable quantitative measure of atherosclerosis. A genomewide linkage analysis was conducted to localize a quantitative-trait locus (QTL) influencing carotid IMT. Carotid IMT was measured in 596 men and 629 women from 311 extended families (1,242 sib pairs) in the Framingh...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/381559
更新日期：2004-02-01 00:00:00
abstract：:HLA class II loci are useful markers in human population genetics, because they are extremely variable and because new molecular techniques allow large-scale analysis of DNA allele frequencies. Direct DNA typing by hybridization with sequence-specific oligonucleotide probes (HLA oligotyping) after enzymatic in vitro P...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1992-09-01 00:00:00
abstract：:Monosomy for the X chromosome in humans creates a genetic Achilles' heel for nature to deal with. We report that the human X chromosome appears to have one-third the density of the coding sequence of the autosomes and, because of partial shielding from the high mutation rate of the male sex, that it should also have a...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/303010
更新日期：2000-08-01 00:00:00
abstract：:Permanent teeth of 12 individuals with a 47,XYY chromosome constitution have been examined. The tooth sizes of 47,XYY males were found to be larger than those of control males and females. In many instances the differences were statistically significant. Using these results, it was possible to conclude that a factor ...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1975-01-01 00:00:00
abstract：:Dominant congenital spinal muscular atrophy (DCSMA) is a disorder of developing anterior horn cells and shows lower-limb predominance and clinical overlap with hereditary spastic paraplegia (HSP), a lower-limb-predominant disorder of corticospinal motor neurons. We have identified four mutations in bicaudal D homolog ...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2013.04.018
更新日期：2013-06-06 00:00:00
abstract：:A previously unrecognized autosomal dominant syndrome affecting oral, nasal, vaginal, urethral, anal, bladder, and conjunctival mucosa with cataracts, follicular keratosis, nonscarring alopecia, and terminal lung disease is described in a four-generation kindred of German extraction. Severe photophobia, tearing, and n...
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：:Syndromic diarrhea (or trichohepatoenteric syndrome) is a rare congenital bowel disorder characterized by intractable diarrhea and woolly hair, and it has recently been associated with mutations in TTC37. Although databases report TTC37 as being the human ortholog of Ski3p, one of the yeast Ski-complex cofactors, this...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2012.02.009
更新日期：2012-04-06 00:00:00
abstract：:DNA length polymorphism in the 5'-flanking region of the human insulin gene has been reported by Bell et al. (1981), Rotwein et al. (1981), and Owerbach and Nerup (1982). Bgl I digestions of human DNA that have been hybridized to an insulin probe using the Southern technique shows that there are two distinct groups of...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1983-03-01 00:00:00
abstract：:Assignment of a susceptibility locus for cutaneous malignant melanoma-dysplastic nevus (CMM/DN) to chromosome 1p remains controversial. We examined the relationship between CMM/DN and markers D1S47, PND, and D1S160 on seven new families (set B) plus updated versions of six previously reported families (set A). Three l...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1993-03-01 00:00:00
abstract：:Personalized genetic information is not widely utilized as a resource in learning environments, in part because of concerns about data privacy and the treatment of sensitive personal information. Here we describe the implementation of a curriculum centered on analyzing personalized genetic-ancestry test results during...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2019.01.001
更新日期：2019-02-07 00:00:00
abstract：:Two of the three class I alcohol dehydrogenase (ADH) genes (ADH2 and ADH3) encode known functional variants that act on alcohol with different efficiencies. Variants at both these genes have been implicated in alcoholism in some populations because allele frequencies differ between alcoholics and controls. Specificall...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/302317
更新日期：1999-04-01 00:00:00
abstract：:Some genes that affect development and behavior in mammals are known to be imprinted; and > or = 1% of all mammalian genes are imprinted. Hence, incorporating an imprinting parameter into linkage analysis may increase the power to detect linkage for these traits. Here we propose theoretical justifications for a recent...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/338931
更新日期：2002-03-01 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：:Epileptic encephalopathy (EE) refers to a clinically and genetically heterogeneous group of severe disorders characterized by seizures, abnormal interictal electro-encephalogram, psychomotor delay, and/or cognitive deterioration. We ascertained two multiplex families (including one consanguineous family) consistent wi...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2014.06.006
更新日期：2014-07-03 00:00:00
abstract：:With the imminent availability of ultra-high-volume genotyping platforms (on the order of 100,000-1,000,000 genotypes per sample) at a manageable cost, there is growing interest in the possibility of conducting genomewide association studies for a variety of diseases but, so far, little consensus on methods to design ...
journal_title：American journal of human genetics
pub_type： 杂志文章,评审
doi：10.1086/432962
更新日期：2005-09-01 00:00:00
abstract：:Helicobacter pylori is considered the most prevalent infectious agent among humans, and it causes gastric inflammation, gastroduodenal ulcers, and a risk of gastric cancer. We performed a genomewide linkage analysis among Senegalese siblings phenotyped for H. pylori-reactive serum immunoglobulin G. A multipoint LOD sc...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/367714
更新日期：2003-02-01 00:00:00
abstract：:Epidermolysis bullosa simplex (EBS) is a dominantly inherited genodermatosis characterized by intraepidermal blister formation. Recent reports have suggested that EBS mutations may relate to keratin abnormalities. In this study, we conducted RFLP analyses to test the hypothesis that EBS is linked to one of the keratin...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1991-11-01 00:00:00
abstract：:Linkage markers at or close to the genes encoding the three major fibrillar collagens were used to analyze the segregation of these loci in six pedigrees with dominantly inherited Marfan syndrome. Four pedigrees were discordant at one of the Type I collagen loci (COL1A2), and, of these, two were discordant at the othe...
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：:Bulimia nervosa (BN) is strongly familial, and additive genetic effects appear to contribute substantially to the observed familiality. In turn, behavioral components of BN, such as self-induced vomiting, are reliably measured and heritable. To identify regions of the genome harboring genetic variants conferring susce...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/345801
更新日期：2003-01-01 00:00:00
abstract：:The association between HLA-DR and -DQ and insulin-dependent diabetes mellitus (IDDM) in a defined high-incidence area was analyzed in a total of 58 population-based patients, representing 77% of IDDM patients with age at onset below 16 years, and in 92 unrelated parents in control families without IDDM. HLA haplotype...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1993-07-01 00:00:00
abstract：:We consider sequential sampling of pedigrees for genetic analysis. Cannings and Thompson (1977) gave simple, general guidelines for valid sequential sampling schemes. We show that their formulation of the likelihood contains an error, which is, however, easily corrected so as to maintain the validity of the sequential...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1986-08-01 00:00:00
abstract：:The mean and standard deviation of the first arrival time for a single mutant to reach a certain frequency and the mean age of a mutant persisting in a population have been studied using diffusion methods. These quantities are shown to be highly dependent on both the heterozygous effect and the population size. For pa...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1975-05-01 00:00:00
abstract：:Recently, a new locus (PARK8) for autosomal dominant parkinsonism has been identified in one large Japanese family. Linkage has been shown to a 16-cM centromeric region of chromosome 12, between markers D12S1631 and D12S339. We tested 21 white families with Parkinson disease and an inheritance pattern compatible with ...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/380647
更新日期：2004-01-01 00:00:00
abstract：:We extend the methodology for family-based tests of association and linkage to allow for both variation in the phenotypes of subjects and incorporation of covariates into general-score tests of association. We use standard association models for a phenotype and any number of predictors. We then construct a score stati...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/302782
更新日期：2000-02-01 00:00:00
abstract：:The pheochromocytomas are an important cause of secondary hypertension. Although pheochromocytoma susceptibility may be associated with germline mutations in the tumor-suppressor genes VHL and NF1 and in the proto-oncogene RET, the genetic basis for most cases of nonsyndromic familial pheochromocytoma is unknown. Rece...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/321282
更新日期：2001-07-01 00:00:00
