摘要:

AbstractThe purpose of the review is to describe a system of human erythrocyte membrane glycoproteinsexhibiting extensive diversity. Glycophorins A and B (GPA and GPB) are the antigens of the MNSsblood groups; thus individuals bearing variant glycophorins can be readily identified by serologicaltyping. Examination of the wide array of variants of these antigens showed that they include manyforms, possibly made evident by lack of constraints due to the apparent dispensability of the parentmolecules. This article reviews the molecular genetics of 25 variants of the glycophorin gene family, whose common denominator is that they arise from unequal gene recombinations or gene conversionscoupled to splice‐site mutations. Most rearrangements occurred within a 2‐kb region mainly within GPA and GPB of the gene family and only rarely within the third member, GPE. The key feature isthe shuffling of sequences within two specific exons (one of which is silent), homologous in the twoparent genes. This has resulted in expression of a mosaic of sequences within this region, leading topolymorphism.The common pattern of recombinations coupled to pre‐mRNA splicing was the predominant mechanism of the origin of glycophorin diversity. Thus far this mechanism appears to be unique amonghuman gene families. It could have occurred by chance rearrangements among closely linked genes andbeen driven by a biological advantage, not as yet identified. This remains to be established. Nevertheless, gene rearrangements observed here are akin to those reported for the major histocompatibilitycomplex (MHC). In the glycophorin family the small size of the region within which gene interactionshave occurred and the participation of essentially only two alleles makes this relatively simpler systemmore focused and easier to dissect and describe molecularly. © 1995 Wiley‐L

ISSN:1059-7794    

DOI:10.1002/humu.1380060302

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1995

数据来源: WILEY

摘要:

AbstractMutations in the human aldolase B gene that result in hereditary fructose intolerance have been characterized extensively. Although the majority of subjects have been from northern Europe, subjects from other geographical regions and ethnic groups have been identified. At present 21 mutations have been reported; 15 of these are single base substitutions, resulting in nine amino acid replacements, four nonsense codons, and two putative splicing defects. Two large deletions, two four‐base deletions, a single‐base deletion, and a seven‐base deletion/one‐base insertion have been found. This last mutation leads to a defect in splicing and it is likely that one of the small deletions does as well. Regions of the enzyme where mutations have been observed recurrently are encoded by exons 5 and 9. Indeed, the three most common mutations are found in these exons. Two of these prevalent HFI mutations arose from a common ancestor and spread throughout the population by genetic drift. This finding was based on linkage to two sequence polymorphisms, which are among very few informative polymorphic markers that have been identified within the aldolase B gene. Because of the prevalence of a few HFI alleles, and the recent advances in molecular methods for identifying and screening for mutations, the diagnosis of HFI by molecular screening methods should become routine. These molecular diagnostic methods will be extremely beneficial for this often difficult to diagnose and sometimes fatal disease. © 1995 Wiley

ISSN:1059-7794    

DOI:10.1002/humu.1380060303

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1995

数据来源: WILEY

摘要:

AbstractCystic fibrosis (CF) is caused by mutations in the gene for the cystic fibrosis transmembrane conductance regulator (CFTR) that codes for a cAMP‐regulated chloride channel. The R347P is a missensemutation located within the first membrane spanning domain (MSD1,) of the CFTR protein. This mutation occurs with an overall worldwide frequency of about 0.2%. The patients, originally described with this mutation were compound heterozygotes with the ΔF508 mutation and had a very mild course of CF, suggesting that R347P, similar to other missense mutations affecting the MSDl domain, causes a mild phenotype. We report here a group of 19 CF patients with the R347P mutation of German, Bulgarian, Czech, and Slovak origin, including two homozygotes. Most patients presented with early disease onset, pancreas insufficiency (PI), and early pulmonary involvement, suggesting that this mutation can lead to a severe course of CF. Most R347P alleles in the group studied share a common polymorphic haplotype. In addition, these analyses gave evidence for recurrence of the mutation in two CF patients of German and Czech origin. © 1995 Wiley‐Liss

ISSN:1059-7794    

DOI:10.1002/humu.1380060304

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1995

数据来源: WILEY

摘要:

AbstractMedium‐chain acyl‐CoA dehydrogenase (MCAD) deficiency is a potentially lethal inherited defect in the β‐oxidation of fatty acids. By comparing the behaviour of five missense MCAD mutant proteins expressed in COS cells and inEscherichia coli, we can define some of these as “pure folding mutants.” Upon expression inE. coli, these mutant proteins produce activity levels in the range of the wild‐typeenzyme only if the chaperonins GroESL are co‐overproduced. When Over expressed in COS cells, the pure folding mutants display enzyme activities comparable to the wild‐type enzyme. The results suggest that the MCAD mutations can be modulated by chaperones, a phenomenon that may influence the manifestation of the MCAD disease. © 199

ISSN:1059-7794    

DOI:10.1002/humu.1380060305

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1995

数据来源: WILEY

摘要:

AbstractAllele‐specific polymorphism (ASAP) analysis is a modification of single‐strand conformation polymorphism (SSCP) mutation screening under optimized temperature conditions in a minigel format withethidium bromide detection. ASAP analysis was used to screen for and identify mutations within thehuman thryoid hormone receptor‐ß (hTR‐ß) gene. These mutations are the underlying cause ofresistance to thyroid hormone (RTH). Eleven dissimilar known hTR‐ß mutations and six previouslyuncharacterized mutations were accurately identified. ASAP screening extends to unique ASAP‐DNAfingerprinting as an identifying signature for each novel hTR‐ß mutation detected thus far. Gel‐plugsfrom the SSCP gels containing polymorphic single‐stranded DNA alleles were used without elution toprepare solid‐phase sequencing templates for mutant allele PCR and sequencing (MAPS). The couplingof ASAP analysis with MAPS has eliminated many of the interpretative and technical problemsassociated with the sequencing of heterozygous alleles. Together, this convenient screening and sequencing methodology offers accuracy, reproducibility, speed, and the potential elimination of allradioactivity, providing a general strategy for future automated detection and characterization of genetic mutations.

ISSN:1059-7794    

DOI:10.1002/humu.1380060306

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1995

数据来源: WILEY

摘要:

AbstractFamilial hypercholesterolemia (FH) has an estimated frequency of 1:154 among French Canadians in Northeastern Quebec, compared with 1:500 in most other populations. FH is caused by numerous mutations of the low‐density lipoprotein (LDL) receptor gene, but only six well‐characterized mutations are known to cause FH in French Canadians. High prevalence of the phenotype, along with a limited number of mutations in this population, provides a unique opportunity to study genotype‐phenotype variation. Since the current methods for detection of point mutations in this population use complicated approaches, we report polymerase chain reaction (PCR)‐based restriction fragment analysis to detect all four point mutations. This approach provides a rapid diagnosis and is suitable to screen large number of samples for studies in genetic epidemiology; it should be useful in identifying FH in other populations bearing the same mutations. © 1995 Wiley

ISSN:1059-7794    

DOI:10.1002/humu.1380060307

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1995

数据来源: WILEY

ISSN:1059-7794    

DOI:10.1002/humu.1380060308

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1995

数据来源: WILEY

ISSN:1059-7794    

DOI:10.1002/humu.1380060309

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1995

数据来源: WILEY

ISSN:1059-7794    

DOI:10.1002/humu.1380060310

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1995

数据来源: WILEY

ISSN:1059-7794    

DOI:10.1002/humu.1380060311

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1995

数据来源: WILEY