摘要:

SUMMARYWe have now determined the molecular genetic basis for the common biochemical polymorphism at the adenosine deaminase (ADA) locus. The ADA*2 allele contains a G to A transition at nt22 (relative to the ATG) that results in substitution of asparagine for aspartic acid at codon 8 (Asp8Asn). Introduction of the nucleotide substitution into an ADA 1 cDNA and transfection into monkey kidney (Cos) cells confirmed that the mutation resulted in expression of an enzyme that comigrated with the naturally occurring ADA 2 allozyme. The substitution of neutral asparagine for anionic aspartic acid is consistent with the more cathodal electrophoretic migration of ADA 2 as compared with ADA 1. The nucleotide substitution was found on at least two different genetic backgrounds, suggesting independent recurrence of the mutation. Consistent with independent recurrence, the G to A transition is at a CpG dinucleotide and represents a type of mutation that occurs with high frequency. We have also unexpectedly identified a probable intragenic crossover in the very large first intron that is rich in repetitive DNA sequences.

ISSN:0003-4800    

DOI:10.1111/j.1469-1809.1994.tb00720.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

SUMMARYUsing high resolution isoelectric focusing, α1‐antitrypsin phenotypes were studied in 106 individuals of the PI ZZ genotype including 71 with liver disease, 22 with chest disease and 13 healthy subjects. The resulting Z patterns were found to be highly variable. In the majority of cases (89/106) the maximum staining intensity was either in the most basic isoform or shared equally between two basic isoforms of the Z phenotype. However, in 17 cases there was a marked intensification of the more acidic isoforms resulting in a pattern which closely resembled the SZ phenotype. This ‘SZ like’ pattern occurred more frequently in the liver group (16/71) than the chest group (0/22) or healthy (1/13) controls. One possible consequence of the ‘SZ like’ pattern is confusion with the genuine SZ phenotype leading to misclassification. If this were so, there could be an erroneous exaggeration of the actual incidence of childhood liver disease associated

ISSN:0003-4800    

DOI:10.1111/j.1469-1809.1994.tb00721.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

SUMMARYWe have investigated the arrangement of genes in the rare Rh (Rhesus) partial null condition D–, Southern blot and PCR studies under conditions which distinguish the highly homologous RH D and RH C/E genes show that in an Icelandic family with the D– haplotype at least 85% of the RH C/E gene is deleted. This finding is in contrast to one other published case of this phenotype, where intact RH D and C/E genes were found, and also to the full amorph Rhnullphenotype, where an intact RH C/E gene was found, accompanied by the deletion of the RH D gene typical of Rh D‐negative indivi

ISSN:0003-4800    

DOI:10.1111/j.1469-1809.1994.tb00722.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

SUMMARYWe report the identification and characterization of a clone for the DNA binding proteinSON, which we have isolated from a human keratinocyte cDNA library. Using this clone we have found that theSONgene is expressed in different cell types and that homologous sequences can be detected in vertebrate and insect genomic DNA. Using the polymerase chain reaction (PCR) to amplifySONsequences from a panel of somatic cell hybrids we have assigned the gene encoding humanSONto chromosome 21. By use of hybrids containing regions of chromosome 21 the localization has been refined to 21q 22. 1‐q22.

ISSN:0003-4800    

DOI:10.1111/j.1469-1809.1994.tb00723.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

SUMMARYA new method is described for employing family data to test for significant haplotype effects on continuously distributed variables, using likelihood‐ratio tests of linear models in which haplotype effects are parameterized and familial correlations taken into account. The method is applied to the apolipoprotein B (Apo B) gene, using 5 polymorphisms (Insertion/deletion, Bsp1286I,XbaI,MspI,EcoRI) to define haplotypes in 121 French nuclear families. Eleven haplotypes were found, five of which, combined, account for over 95% of the sample. A haplotype phylogeny is proposed, and is used to define a nested set of models for testing the effects of Apo B variation on total‐, low‐density‐lipoprotein (LDL)‐, and high‐density ‐lipoprotein (HDL)‐cholesterol, triglyceride, and Apo B levels. Apo B haplotype effects account for about 10% of the genetic variance and 5% of the total variance in HDL‐cholesterol and triglyceride levels. Clusters of evolutionarily‐related haplotypes with similar phenotypic effects are identified for HDL‐cholesterol and triglycerides. Single haplotypes with statistically significant effects are identified for cholesterol, LDL‐choles

ISSN:0003-4800    

DOI:10.1111/j.1469-1809.1994.tb00724.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

SUMMARYBecause of the difficulty of performing full likelihood analysis over multiple loci and the large numbers of possible orders, a number of methods have been proposed for quickly evaluating orders and, to a lesser extent, for generating good orders. A new method is proposed which uses a function which is moderately laborious to compute, the sum of lod scores between all pairs of loci. This function can be smoothly minimized by initially allowing the loci to be placed anywhere in space, and only subsequently constraining them to lie along a one‐dimensional map. Application of this approach to sample data suggests that it has promise and might usefully be combined with other methods when loci need to be ordere

ISSN:0003-4800    

DOI:10.1111/j.1469-1809.1994.tb00725.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

ISSN:0003-4800    

DOI:10.1111/j.1469-1809.1994.tb00726.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

ISSN:0003-4800    

DOI:10.1111/j.1469-1809.1994.tb00727.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY