Parental and chromosomal origin of unbalanced de novo structural chromosome abnormalities in man

Thomas, N. Simon; Durkie, Miranda; Zyl, Berendine van; Sanford, Richard; Potts, Gemma; Youings, Sheila; Dennis, N R; Jacobs, Patricia A.

doi:10.1007/s00439-006-0157-6

Cited by 52 publications

(48 citation statements)

References 16 publications

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“…18,19 In our series, only two of nine deletions in patients, for whom parental-origin data were obtained, were located in the maternal chromosome, which is consistent with the ratio reported previously for interstitial deletions at any site. 44 In another study, de novo imbalances not mediated by low copy repeats were significantly more often of paternal than of maternal origin. 45 Thus, to date, although there is no strong evidence supporting an imprinting mechanism in the 6q16 region, a parent-of-origin effect cannot be excluded, as none of the three maternally derived deletions, which were currently reported, (patient no.…”

Section: Clinical and Fetopathological Datamentioning

confidence: 94%

Incomplete penetrance and phenotypic variability of 6q16 deletions including SIM1

et al. 2014

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4,5,6 6q16 deletions have been described in patients with a Prader-Willi-like (PWS-like) phenotype. Recent studies have shown that certain rare single-minded 1 (SIM1) loss-of-function variants were associated with a high intra-familial risk for obesity with or without features of PWS-like syndrome. Although SIM1 seems to have a key role in the phenotype of patients carrying 6q16 deletions, some data support a contribution of other genes, such as GRIK2, to explain associated behavioural problems. We describe 15 new patients in whom de novo 6q16 deletions were characterised by comparative genomic hybridisation or single-nucleotide polymorphism (SNP) array analysis, including the first patient with fetopathological data. This fetus showed dysmorphic facial features, cerebellar and cerebral migration defects with neuronal heterotopias, and fusion of brain nuclei. The size of the deletion in the 14 living patients ranged from 1.73 to 7.84 Mb, and the fetus had the largest deletion (14 Mb). Genotype-phenotype correlations confirmed the major role for SIM1 haploinsufficiency in obesity and the PWS-like phenotype. Nevertheless, only 8 of 13 patients with SIM1 deletion exhibited obesity, in agreement with incomplete penetrance of SIM1 haploinsufficiency. This study in the largest series reported to date confirms that the PWS-like phenotype is strongly linked to 6q16.2q16.3 deletions and varies considerably in its clinical expression. The possible involvement of other genes in the 6q16.2q16.3-deletion phenotype is discussed.

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Section: Clinical and Fetopathological Datamentioning

confidence: 94%

Incomplete penetrance and phenotypic variability of 6q16 deletions including SIM1

et al. 2014

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“…Although base substitutions are the most frequent paternal genetic abnormalities, it is reported that 80 % of structural chromosomal abnormalities may originate paternally [83,124] ( Table 4). Several studies have suggested that chromosomal deletions and duplications increase with paternal aging [124].…”

Section: Effect Of Paternal Age On Other Diseasesmentioning

confidence: 99%

“…Several studies have suggested that chromosomal deletions and duplications increase with paternal aging [124].…”

Section: Effect Of Paternal Age On Other Diseasesmentioning

confidence: 99%

Effects of aging on the male reproductive system

Güneş

Hekim

Arslan

et al. 2016

J Assist Reprod Genet

190

118

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The study aims to discuss the effects of aging on the male reproductive system. A systematic review was performed using PubMed from 1980 to 2014. Aging is a natural process comprising of irreversible changes due to a myriad of endogenous and environmental factors at the level of all organs and systems. In modern life, as more couples choose to postpone having a child due to various socioeconomic reasons, research for understanding the effects of aging on the reproductive system has gained an increased importance. Paternal aging also causes genetic and epigenetic changes in spermatozoa, which impair male reproductive functions through their adverse effects on sperm quality and count as, well as, on sexual organs and the hypothalamic-pituitarygonadal axis. Hormone production, spermatogenesis, and testes undergo changes as a man ages. These small changes lead to decrease in both the quality and quantity of spermatozoa. The offspring of older fathers show high prevalence of genetic abnormalities, childhood cancers, and several neuropsychiatric disorders. In addition, the latest advances in assisted reproductive techniques give older men a chance to have a child even with poor semen parameters. Further studies should investigate the onset of gonadal senesce and its effects on aging men.

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“…The majority of 115 de novo unbalanced structural chromosome abnormalities detectable by light microscopy are of paternal origin 4 varying from 84% of interstitial deletions to 58% of duplications and rings. Deletions of the long arm of chromosome 18 are disproportionately male 5 as well as the deletions that cause Wolf-Hirschhorn syndrome 6 and Cri-du-chat syndrome.…”

Section: Introductionmentioning

confidence: 99%

Advanced age increases chromosome structural abnormalities in human spermatozoa

et al. 2010

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This study explores the relationship between sperm structural aberrations and age by using a multicolor multichromosome FISH strategy that provides information on the incidence of duplications and deletions on all the autosomes. ToTelvysion kit (Abbott Molecular, Abbott Park, IL, USA) with telomere-specific probes was used. We investigated the sperm of 10 male donors aged from 23 to 74 years old. The donors were divided into two groups according to age, a cohort of five individuals younger than 40 and a cohort of five individuals older than 60 years. The goal of this study was to determine (1) the relationship between donor age and frequency and type of chromosome structural abnormalities and (2) chromosomes more frequently involved in sperm structural aberrations. We found that the older patients had a higher rate of structural abnormalities (6.6%) compared with the younger cohort (4.9%). Although both duplications and deletions were seen more frequently in older men, our findings demonstrate the presence of an excess of duplications versus deletions in both groups at a ratio of 2 to 1. We demonstrate that the distribution of duplications and deletions was not linear along the chromosomes, although a trend toward a higher rate of abnormalities in larger chromosomes was observed. This work is the first study addressing the frequencies of sperm chromosome structural aberrations of all autosomes in a single assay thus making a contribution to the clarification of the amount and origin of damage present in human spermatozoa and in relation to age.

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Parental and chromosomal origin of unbalanced de novo structural chromosome abnormalities in man

Cited by 52 publications

References 16 publications

Incomplete penetrance and phenotypic variability of 6q16 deletions including SIM1

Incomplete penetrance and phenotypic variability of 6q16 deletions including SIM1

Effects of aging on the male reproductive system

Advanced age increases chromosome structural abnormalities in human spermatozoa

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