Genetic polymorphism in the intron of the growth hormone gene of the bleak

Comparison of nucleotide sequences of the growth hormone gene of two populations of bleak from the Main Donau Rivers, Southern Germany, revealed an A/T point mutation resulting in an AluI restriction fragment length polymorphism. The frequencies of alleles T and A are 0–95/0–05 in the Donau and 0–62/0–38 in the Main.     

Evidence for extensive polymorphism of RT1 Class II molecules in the rat

RT1.B Class II molecules, comparable to I-A and I-E molecules in mice, have been characterized by two-dimensional (2D) gel electrophoresis for seven rat strains expressing different RT1 haplotypes. RT1.B molecules were immunoprecipitated from radiolabeled rat lymphocyte preparations with mouse monoclonal antibodies reactive with mouse I-Ab antigens and I-Ek antigens. For each RT1 haplotype, two I-A-like subunits, alpha and beta, and two I-E-like subunits, gamma and delta, have been identified. 2D gel analysis of RT1.B molecules from different strains in paired combinations reveals that, with a few notable exceptions, the alpha, beta, and delta subunits associated with different RT1 haplotypes are characterized by unique 2D gel spot patterns. In contrast, the gamma subunits of all RT1.B haplotypes appear identical. This evidence confirms and extends our previous analysis of RT1.B molecules by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and suggests a high level of polymorphism for genes in the RT1.B region, with the exception of the RT1.Bc gene encoding gamma. Interestingly, three rat strains appear exceptional in the identity of their alpha, gamma, and delta subunits, which suggests that these strains express closely related RT1 haplotypes derived from a common progenitor.     

Association of cattle growth hormone gene polymorphism with milk productivity

Polymorphisms in two growth hormone (GH) gene regions, intron 3 (MspI-polymorphism) and exon 4 (AluI polymorphism), and their association with milk productivity in Black Pied, Bestuzhevskaya, and Simmental cattle breeds have been studied. It was shown that allele GH ^V at the AluI polymorphic site and allele GH ^D at the MSPI polymorphic site of the GH gene, particularly in homozygous state, were more favorable in terms of agricultural importance than the GH ^L and GH ^C alleles.     

Evolution of the proximal promoter region of the mammalian growth hormone gene.

The evolutionary relationship between the proximal growth hormone (GH) gene promoter sequences of 12 mammalian species was explored by comparison of their trinucleotide composition and by multiple sequence alignment. Both approaches yielded results that were consistent with the known fossil record-based phylogeny of the analysed sequences, suggesting that the two methods of tree reconstruction might be equally efficient and reliable. The pattern of evolution inferred for the mammalian GH gene promoters was found to vary both temporally and spatially. Thus, two distinct regions devoid of any evolutionary changes exist in primates, but only one of these 'gaps' is also observed in rodents, and neither is seen in ruminants. Furthermore, different evolutionary rates must have prevailed during different periods of evolutionary time and in different lineages, with a dramatic increase in evolutionary rate apparent in primates. Since a similar pattern of discontinuity has been previously noted for the evolution of the GH-coding regions, it may reflect the action of positive selection operating upon the GH gene as a single cohesive unit. Strong evidence for the action of gene conversion between primate GH gene promoters is provided by the fact that the human GH1 and GH2 sequences, which are thought to have diverged before the divergence of Old World monkeys from great apes, are more similar to one another than either is to the rhesus monkey GH2 promoter. Finally, it was noted that a number of nucleotide positions in the GH1 gene promoter that are polymorphic in humans appear to be highly conserved in mammals. This apparent conundrum, which could represent a caveat for the interpretation of phylogenetic footprinting studies, is potentially explicable in terms either of reduced genetic diversity in highly inbred animal species or insufficient population data from non-human species.     

Novel restriction fragment length polymorphism of the growth hormone gene in inbred rats

A novel restriction fragment length polymorphism in inbred rats was detected by Southern blot analysis with rat growth hormone cDNA as a probe. Four alleles, characterized by PstI fragments of 1.2, 1.1, 0.9, and 0.7 kb, respectively, were detected in 27 strains examined. The same distribution of polymorphisms was observed on digestion of DNAs of these strains with three other enzymes, PvuII, HindIII, and BamHI. Moreover, the same differences in length of allelic restriction fragments were obtained with these restriction enzymes as with PstI. These findings suggested that the polymorphism was caused by insertion or deletion of variable DNA segments in the second intron of the growth hormone gene. Linkage analyses using backcross progeny provided no evidence for close linkage between the restriction fragment length polymorphism locus and 10 other loci examined.     

The DNA sequence of the H-2kb gene: evidence for gene conversion as a mechanism for the generation of polymorphism in histocompatibilty antigens

We have determined the DNA sequence of the H-2Kb gene of the C57B1/10 mouse. Comparison of this sequence with that of the allelic H-2Kd shows surprisingly that the exons have accumulated more mutations than their introns. Moreover, many of these changes in the exons are clustered in short regions or hot spots. Additional comparison of these sequences with the H-2Ld and H-2Db sequences shows that, in several cases, the altered sequence generated at the hot spot is identical to the corresponding region of a non-allelic H-2 gene. The clustered changes are responsible for 60% of the amino acid differences between the H-2Kb and H-2Kd genes and suggest that micro-gene conversion events occurring within the exons and involving only tens of nucleotides are an important mechanism for the generation of polymorphic differences between natural H-2 alleles.     

The DNA sequence of the H-2K gene: evidence for gene conversion as a mechanism for the generation of polymorphism in histocompatibility antigens

[This corrects the article on p. 453 in vol. 2, PMID: 11894963.].     

Evidence for intrachromosomal gene conversion in cultured mouse cells

In this report we present an experimental scheme that facilitates the study of homologous recombination between closely linked genes in cultured mammalian cells. Two different Xho I linker insertion mutants of the herpes simplex virus type 1 thymidine kinase (HTK) gene were introduced into mouse LTK^? cells as direct repeats on a plasmid carrying a dominant selectable marker. Following stabilization of these sequences in the recipient cell, selection for TK⁺ was applied to detect recombinational events between different TK^? genes. TK⁺ segregants were observed at a frequency of 10^?4–10^?5 in lines harboring both mutant genes. Control lines carrying only one type of mutant HTK gene yielded TK⁺ cells at frequencies of 10^?7 or less. Physical analysis of the TK⁺ segregants has revealed the presence of an apparently normal HTK gene that is resistant to Xho I endonuclease digestion in each TK⁺ line examined. Analyses of the TK gene pairs before and after recombination suggest that at least 50% of the recombinants are the result of nonreciprocal exchanges of genetic information, or gene conversion events.     

HLA-DRA promoter polymorphism and diversity generation within the immune system

Multiple major histocompatibility complex (MHC) alleles exist at most class I and II loci. Polymorphism of MHC polypeptides may reflect either different levels of selective pressure operating on each molecule or different mutation rates at different loci. To gain further insight into this issue, we sequenced the non-coding promoter region of the HLA-DRA gene from several Epstein-Barr virus-transformed B cell lines and compared the extent of polymorphism found in this region with the known polymorphism of the HLA-DQB promoter. Our results indicate that the HLA-DRA promoter displays a low level of polymorphism while the promoter of HLA-DQB exhibits a nucleotide substitution rate fivefold greater than that of DRA. Moreover, through phylogenetic analysis, the HLA-DRA promoter was found to have diverged much less than the associated alleles of HLA-DRB1 and -DQA1. Taken together, these results suggest that the HLA-DRA promoter is highly conserved and may be under a stronger functional constraint than the promoter regions of other MHC class II genes. Received: 30 May 1996 / Revised: 24 January 1997     

The duplicated gene copy of the ovine growth hormone gene contains a PvuII polymorphism in the second intron

PvuII restriction fragment length polymorphism (RFLP) was found at the growth hormone locus in sheep carrying the GH2 allele where the gene is duplicated. By restriction analysis and using the polymerase chain reactibn we demonstrated that this RFLP is due to a mutation at the Pvu II site located in the second intron of the 3′ copy of the GH2 allele.     

Evidence for gene conversion in the amylase multigene family of Drosophila pseudoobscura

The alpha-amylase (Amy) multigene family in Drosophila pseudoobscura is located on the third chromosome, which is polymorphic for more than 40 inverted gene arrangements. The number of copies in this family ranges from one to three, depending on the arrangement in question. A previous study of the three Amy genes from the Standard (ST) arrangement suggested either that duplicated copies (Amy2 and Amy3) are functionally constrained or that they are undergoing gene conversion with Amy1. In order to elucidate further the pattern of molecular evolution in this family, we cloned and sequenced four additional Amy genes, two from the Santa Cruz (SC) and two from the Chiricahua (CH) gene arrangement. Of the two alternatives, only the hypothesis of gene conversion is supported by the sequence analysis. The homogenization effect of gene conversion has been strongest in SC, whose copies differ by only two nucleotides, less noticeable in ST, and negligible in the CH. Furthermore, the action of gene conversion is apparently localized, occurring only in the coding region. Interestingly, these results concur with the findings of other workers for the duplicated Amy genes in the Drosophila melanogaster group. Thus, the occurrence of gene conversion in the Amy multigene family seems to be a common feature in the Drosophila species studied so far.      

IFN-gamma promoter gene polymorphism in psoriasis vulgaris.

This study was performed to investigate the association between interferon (IFN)-gamma single nucleotide polymorphism (SNP) and susceptibility for psoriasis vulgaris. DNA from 78 patients with psoriasis vulgaris (54 patients with type I psoriasis, 24 with type II psoriasis) and 74 healthy volunteers was investigated. IFN-gamma promoter gene SNP in position 874 was evaluated by polymerase chain reaction with sequence-specific primers (PCR-SSP) and the results were compared between a group of psoriatic patients, divided into early onset of psoriasis (type I) and late onset of psoriasis (type II) subgroups, and healthy control subjects. A significant difference in the genotype frequencies between psoriasis patients and healthy controls was found (p < 0.02) and no significant differences were observed analyzing subsets of psoriatic patients (gender, type of disease) also in carriage and allele frequencies. The results suggest that IFN-gamma polymorphism is associated with susceptibility to psoriasis vulgaris.