Evidence for gene conversion in the generation of extensive polymorphism in the promoter of the growth hormone gene

Giordano, Mara; Marchetti, Cristina; Chiorboli, E; Bona, Gianni; Richiardi, P.

doi:10.1007/s004390050500

Cited by 63 publications

(68 citation statements)

References 28 publications

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“…Moreover, in studying the relationships of members of a gene family, gene conversion is one commonly invoked explanation when orthologous genes do not form a monophylogeny. Previous studies have identified several gene conversion events in the evolution of the GH gene family (Hirt et al 1987, Chen et al 1989, Giordano et al 1997, Krawczak et al 1999, Horan et al 2003, Mendoza et al 2004, Ye et al 2005. In the present study, we also detected some cases of gene conversion events in NWM by a statistical method.…”

Section: Test Of Variable Among Lineages and Sites By The Maximum-liksupporting

confidence: 74%

Independent origin of the growth hormone gene family in New World monkeys and Old World monkeys/hominoids

Yuan²,

Shi³

et al. 2005

Journal of Molecular Endocrinology

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The growth hormone (GH) gene family represents an erratic and complex evolutionary pattern, involving many evolutionary events, such as multiple gene duplications, positive selection, the birth-and-death process and gene conversions. In the present study, we cloned and sequenced GH-like genes from three species of New World monkeys (NWM). Phylogenetic analysis strongly suggest monophyly for NWM GH-like genes with respect to those of Old World monkeys (OWM) and hominoids, indicating that independent gene duplications have occurred in NWM GH-like genes. There are three main clusters of genes in putatively functional NWM GH-like genes, according to our gene tree.Comparison of the ratios of nonsynonymous and synonymous substitutions revealed that these three clusters of genes evolved under different kinds of selective pressures. Detailed analysis of the evolution of pseudogenes showed that the evolutionary pattern of this gene family in platyrrhines is in agreement with the so-called birth-and-death process.

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Section: Test Of Variable Among Lineages and Sites By The Maximum-liksupporting

confidence: 74%

Independent origin of the growth hormone gene family in New World monkeys and Old World monkeys/hominoids

Yuan²,

Shi³

et al. 2005

Journal of Molecular Endocrinology

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“…We identified a novel polymorphism, a transition from adenine to guanine at nt 69 (A69G), which has been reported as a mutation in patients who are short in stature. 18 Of the other nine SNPs reported in previous studies performed in this region, 13,14 three were common in the current population (Table 1). These 3 SNPs, along with the SNP at nt ϩ69 and the SNP in intron 4, were genotyped using the TaqMan assay (Applied Biosystems) for all participants.…”

Section: Laboratory Protocolsmentioning

confidence: 71%

“…12 The promoter and the proximal region are highly polymorphic, with 9 single-nucleotide polymorphisms (SNPs) reported within a 310 -base pair (bp) stretch. 13,14 It has been reported recently that these polymorphisms (in haplotypes) affect GH1 expression significantly. 13 In addition, an SNP located at bp 1169 (intron 4 [P-1]) of the GH1 gene has been linked to GH1 secretion in a trial involving prepubertal short children.…”

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confidence: 99%

Genetic polymorphisms in the human growth hormone‐1 gene (GH1) and the risk of breast carcinoma

Ren

Cai

Shu

et al. 2004

Cancer

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BACKGROUNDIn addition to possessing many physiologic functions, human growth hormone‐1 (GH1) has been shown in recent in vitro and in vivo experiments to induce malignant disease, including breast carcinoma. The authors investigated the association of breast carcinoma with genetic polymorphisms in the GH1 gene in the Shanghai Breast Cancer Study.METHODSIncluded in the current investigation were 1193 women with breast carcinoma (case patients) and 1310 healthy women from the same community (control patients) who completed in‐person interviews and provided blood samples. Genetic polymorphisms in the proximal promoter region (nucleotide [nt] −162 to nt +148 relative to the transcription start site of the GH1 gene) were searched and confirmed by resequencing DNA samples from 43 study participants. A novel polymorphism, a transition from adenine to guanine at nt 69 (A69G), was identified. Samples from all participants were genotyped with TaqMan 5′ nuclease assays for five common single‐nucleotide polymorphisms (SNPs)—four in the proximal region (A‐75G, G‐57T, A‐6G, and A69G) and one in intron 4 (T1169A).RESULTSThe frequencies of occurrence for the minor alleles in these polymorphic sites were 0.04, 0.60, 0.24, 0.03, and 0.34, respectively, in the control group; these frequencies were comparable to those observed in the case group. After adjusting for potential confounding factors, none of the SNPs investigated in this study showed a statistically significant association with breast carcinoma risk. This null association was found for both younger women (age < 45 years) and older women (age ≥ 45 years). GH1 gene haplotypes were assessed using SNP data and were analyzed in relation to breast carcinoma risk. Again, none of the haplotypes were associated with breast carcinoma risk.CONCLUSIONSThe results of the current study suggest that genetic polymorphisms in the proximal promoter region and in the fourth intron of the GH1 gene are unrelated to breast carcinoma risk in Chinese women. Cancer 2004. © 2004 American Cancer Society.

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“…In addition, it is possible that, owing to the low number of compared BAC clones, many SNPs may not have been discovered, particularly low-frequency SNPs. The increased polymorphism in segmental duplications can be explained either by gene conversion with other LCRs found in the genome (Giordano et al 1997;Hurles 2002;Hurles et al 2004) or by selective pressure on sequence diversification and suppression of deleterious recombination between LCR22-2 and LCR22-4.…”

Section: Genome Research 1491mentioning

confidence: 99%

Traffic of genetic information between segmental duplications flanking the typical 22q11.2 deletion in velo-cardio-facial syndrome/DiGeorge syndrome

et al. 2005

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Velo-cardio-facial syndrome/DiGeorge syndrome results from unequal crossing-over events between two 240-kb low-copy repeats termed LCR22 (LCR22-2 and LCR22-4) on Chromosome 22q11.2, comprised of modules, each of which are >99% identical in sequence. To delineate regions in the LCR22s that might contain hotspots for 22q11.2 rearrangements, we scanned the interval for increased rates of recombination with the hypothesis that these regions might be more prone to breakage. We generated an algorithm to detect sites of altered recombination by searching for single nucleotide polymorphic positions in BAC clones from different libraries mapped to LCR22-2 and LCR22-4. This method distinguishes single nucleotide polymorphisms from paralogous sequence variants and complex polymorphic positions. Sites of shared polymorphism are considered potential sites of gene conversion or double cross-over between the two LCR22s. We found an inverse correlation between regions of paralogous sequence variants that are unique to a given position within one LCR22 and clusters of shared polymorphic sites, suggesting that these clusters depict altered recombination and not remnants of ancestral single nucleotide polymorphisms. We postulate that most shared polymorphic sites are products of past transfers of DNA information between the LCR22s, suggesting that frequent traffic of genetic material may induce genomic instability in the two LCR22s. We also found that gaps up to 1.5 kb long can be transferred between LCR22s.

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Evidence for gene conversion in the generation of extensive polymorphism in the promoter of the growth hormone gene

Cited by 63 publications

References 28 publications

Independent origin of the growth hormone gene family in New World monkeys and Old World monkeys/hominoids

Independent origin of the growth hormone gene family in New World monkeys and Old World monkeys/hominoids

Genetic polymorphisms in the human growth hormone‐1 gene (GH1) and the risk of breast carcinoma

Traffic of genetic information between segmental duplications flanking the typical 22q11.2 deletion in velo-cardio-facial syndrome/DiGeorge syndrome

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