Abstract:
:Fanconi anemia (FA) is an autosomal recessive disease characterized by progressive pancytopenia, congenital malformations, and predisposition to acute myeloid leukemia. At least five complementation groups (FA-A-FA-E) have been identified. The relative prevalence of FA-A has been estimated at an average of approximately 65% but may widely vary according to ethnic background. In Italy, 11 of 12 patients analyzed by cell-fusion studies were assigned to group FA-A, suggesting an unusually high relative prevalence of this FA subtype in patients of Italian ancestry. We have screened the 43 exons of the FAA gene and their flanking intronic sequences in 38 Italian FA patients, using RNA-SSCP. Ten different mutations were detected: three nonsense and one missense substitutions, four putative splice mutations, an insertion, and a duplication. Most of the mutations are expected to cause a premature termination of the FAA protein at various sites throughout the molecule. Four protein variants were also found, three of which were polymorphisms. The missense mutation D1359Y, not found in chromosomes from healthy unrelated individuals, was responsible for a local alteration of hydrophobicity in the FAA protein, and it was likely to be pathogenic. Thus, the mutations so far encountered in the FAA gene are essentially all different. Since screening based on the analysis of single exons by genomic DNA amplification apparently detects only a minority of the mutations, methods designed to detect alterations in the genomic structure of the gene or in the FAA polypeptide may be helpful in the identification of FAA mutations.
journal_name
Am J Hum Genetjournal_title
American journal of human geneticsauthors
Savino M,Ianzano L,Strippoli P,Ramenghi U,Arslanian A,Bagnara GP,Joenje H,Zelante L,Savoia Adoi
10.1086/301632subject
Has Abstractpub_date
1997-12-01 00:00:00pages
1246-53issue
6eissn
0002-9297issn
1537-6605pii
S0002-9297(07)60224-9journal_volume
61pub_type
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journal_title:American journal of human genetics
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abstract::Experiments designed to illuminate the mechanism by which folic acid and thymidine inhibit expression of the Xq28 fragile site in human lymphocytes are described. The fragile site is induced by 5-fluorodeoxyuridine (FUdR), a potent inhibitor of thymidylate synthetase, in the presence of otherwise inhibiting concentrat...
journal_title:American journal of human genetics
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abstract::There are three endogamous subdivisions of the Hutterite population, a North American religious isolate. These individuals live on communal farms, and residence is strictly patrilocal. We report on the distributions of HLA-A and B alleles and haplotypes in 203 married women from one subdivision--the Dariusleut--in Alb...
journal_title:American journal of human genetics
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更新日期:1980-03-01 00:00:00
abstract::The May-Hegglin anomaly (MHA) is an autosomal dominant platelet disorder of unknown etiology. It is characterized by thrombocytopenia, giant platelets, and leukocyte inclusion bodies, and affected heterozygotes are predisposed to bleeding episodes. The MHA gene has recently been localized, by means of linkage analysis...
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abstract::Living at high altitude is one of the most difficult challenges that humans had to cope with during their evolution. Whereas several genomic studies have revealed some of the genetic bases of adaptations in Tibetan, Andean, and Ethiopian populations, relatively little evidence of convergent evolution to altitude in di...
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journal_title:American journal of human genetics
pub_type: 杂志文章
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更新日期:1993-10-01 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
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journal_title:American journal of human genetics
pub_type: 杂志文章
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更新日期:1990-12-01 00:00:00
abstract::Familial amyotrophic lateral sclerosis (FALS) affects 5%-10% of cases of amyotrophic lateral sclerosis (ALS) and is inherited as an autosomal dominant condition with incomplete penetrance. One-fifth of these cases of FALS are associated with mutations in copper/zinc-dependent superoxide dismutase (SOD1), but the gene ...
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journal_title:American journal of human genetics
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journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1990-07-01 00:00:00
abstract::Rupture of intracranial aneurysms (IAs) causes subarachnoid hemorrhage, a devastating condition with high morbidity and mortality. Angiographic and autopsy studies show that IA is a common disorder, with a prevalence of 3%-6%. Although IA has a substantial genetic component, little attention has been given to the gene...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/323614
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journal_title:American journal of human genetics
pub_type: 杂志文章
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更新日期:1995-02-01 00:00:00
abstract::To identify Chinese geneticists' views of ethical issues in genetic testing and screening, a national survey was conducted. Of 402 Chinese geneticists asked to participate, 255 (63%) returned by mail anonymous questionnaires. The majority of respondents thought that genetic testing should be offered in the workplace f...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/302020
更新日期:1998-09-01 00:00:00
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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
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journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2019.02.018
更新日期:2019-04-04 00:00:00
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journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2016.06.014
更新日期:2016-08-04 00:00:00
abstract::Case-control studies compare marker-allele distributions in affected and unaffected individuals, and significant results suggest linkage but may simply reflect population structure. For markers with m alleles (m > or = 2), a McNemar-like statistic, I, estimates the level of population association between marker and di...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1997-03-01 00:00:00
abstract::Genetic loci for X-linked retinitis pigmentosa (XLRP) have been mapped between Xp11.22 and Xp22.13 (RP2, RP3, RP6, and RP15). The RP3 gene, which is responsible for the predominant form of XLRP in most Caucasian populations, has been localized to Xp21.1 by linkage analysis and the map positions of chromosomal deletion...
journal_title:American journal of human genetics
pub_type: 杂志文章
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更新日期:1996-07-01 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::Molecular analysis of the human beta-galactosidase gene revealed six different mutations in 10 of 11 Japanese GM1-gangliosidosis patients. They were the only abnormalities in each allele examined in this study. A 165-nucleotide duplication (positions 1103-1267) was found in two infantile patients, producing an abnorma...
journal_title:American journal of human genetics
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doi:
更新日期:1991-08-01 00:00:00
abstract::SPG23 is an autosomal-recessive neurodegenerative subtype of lower limb spastic paraparesis with additional diffuse skin and hair dyspigmentation at birth followed by further patchy pigment loss during childhood. Previously, genome-wide linkage in an Arab-Israeli pedigree mapped the gene to an approximately 25 cM locu...
journal_title:American journal of human genetics
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更新日期:2017-02-02 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::The sibship disequilibrium test (SDT) is designed to detect both linkage in the presence of association and association in the presence of linkage (linkage disequilibrium). The test does not require parental data but requires discordant sibships with at least one affected and one unaffected sibling. The SDT has many d...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/302137
更新日期:1998-12-01 00:00:00
abstract::Family-based tests of linkage disequilibrium typically are based on nuclear-family data including affected individuals and their parents or their unaffected siblings. A limitation of such tests is that they generally are not valid tests of association when data from related nuclear families from larger pedigrees are u...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/302957
更新日期:2000-07-01 00:00:00
abstract::Allelic data for the D1S80 locus was obtained by using the PCR and subsequent analysis with a high-resolution, horizontal PAGE technique and silver staining. Compared with RFLP analysis of VNTR loci by Southern blotting, the approach described in this paper offers certain advantages: (1) discrete allele resolution, (2...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1991-01-01 00:00:00
abstract::Eleven normal families with at least four children were studied cytogenetically using the C-band technique to identify polymorphisms in the constitutive heterochromatin of chromosomes 1, 9 and 16. Thirteen individuals showed one or more variants in such chromosomes. The analysis of the segregation ratios in the 35 off...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1976-07-01 00:00:00
abstract::Diffuse panbronchiolitis affecting East Asians is strongly associated with the class I human leukocyte antigen (HLA) alleles. Recent observations suggest that a major disease-susceptibility gene may be located between the HLA-B and HLA-A loci in the class I region of the major histocompatibility complex on chromosome ...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/302786
更新日期:2000-02-01 00:00:00
abstract::Cranial neural crest (CNC) is a multipotent migratory cell population that gives rise to most of the craniofacial bones. An intricate network mediates CNC formation, epithelial-mesenchymal transition, migration along distinct paths, and differentiation. Errors in these processes lead to craniofacial abnormalities, inc...
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pub_type: 杂志文章
doi:10.1016/j.ajhg.2011.01.003
更新日期:2011-02-11 00:00:00