scholarly journals FSHD: copy number variations on the theme of muscular dystrophy

2010 ◽  
Vol 191 (6) ◽  
pp. 1049-1060 ◽  
Author(s):  
Daphne Selvaggia Cabianca ◽  
Davide Gabellini
Keyword(s):  
Muscular Dystrophy ◽  
Copy Number ◽  
Phenotypic Diversity ◽  
Facioscapulohumeral Muscular Dystrophy ◽  
Copy Number Variations ◽  
Common Source ◽  
Epigenetic Events ◽  
Rate Of Progression ◽  
Chromosomal Architecture ◽  
Severity Of The Disease

In humans, copy number variations (CNVs) are a common source of phenotypic diversity and disease susceptibility. Facioscapulohumeral muscular dystrophy (FSHD) is an important genetic disease caused by CNVs. It is an autosomal-dominant myopathy caused by a reduction in the copy number of the D4Z4 macrosatellite repeat located at chromosome 4q35. Interestingly, the reduction of D4Z4 copy number is not sufficient by itself to cause FSHD. A number of epigenetic events appear to affect the severity of the disease, its rate of progression, and the distribution of muscle weakness. Indeed, recent findings suggest that virtually all levels of epigenetic regulation, from DNA methylation to higher order chromosomal architecture, are altered at the disease locus, causing the de-regulation of 4q35 gene expression and ultimately FSHD.

Spectrum of large copy number variations in 26 diverse Indian populations: potential involvement in phenotypic diversity

2011 ◽  
Vol 131 (1) ◽  
pp. 131-143 ◽  
Author(s):  
Pramod Gautam ◽  
◽  
Pankaj Jha ◽  
Dhirendra Kumar ◽  
Shivani Tyagi ◽  
...  
Keyword(s):  
Copy Number ◽  
Phenotypic Diversity ◽  
Copy Number Variations ◽  
Indian Populations

scholarly journals Genome-Wide Assessment Characteristics of Genes Overlapping Copy Number Variation Regions in Duroc Purebred Population

2021 ◽  
Vol 12 ◽  
Author(s):  
Zhipeng Wang ◽  
Yuanyuan Guo ◽  
Shengwei Liu ◽  
Qingli Meng
Keyword(s):  
Copy Number ◽  
Target Genes ◽  
Phenotypic Diversity ◽  
Gene List ◽  
Copy Number Variations ◽  
Structural Variations ◽  
Density Region ◽  
Protein Coding ◽  
Protein Coding Genes ◽  
Strong Negative Selection

Copy number variations (CNVs) are important structural variations that can cause significant phenotypic diversity. Reliable CNVs mapping can be achieved by identification of CNVs from different genetic backgrounds. Investigations on the characteristics of overlapping between CNV regions (CNVRs) and protein-coding genes (CNV genes) or miRNAs (CNV-miRNAs) can reveal the potential mechanisms of their regulation. In this study, we used 50 K SNP arrays to detect CNVs in Duroc purebred pig. A total number of 211 CNVRs were detected with a total length of 118.48 Mb, accounting for 5.23% of the autosomal genome sequence. Of these CNVRs, 32 were gains, 175 losses, and four contained both types (loss and gain within the same region). The CNVRs we detected were non-randomly distributed in the swine genome and were significantly enriched in the segmental duplication and gene density region. Additionally, these CNVRs were overlapping with 1,096 protein-coding genes (CNV-genes), and 39 miRNAs (CNV-miRNAs), respectively. The CNV-genes were enriched in terms of dosage-sensitive gene list. The expression of the CNV genes was significantly higher than that of the non-CNV genes in the adult Duroc prostate. Of all detected CNV genes, 22.99% genes were tissue-specific (TSI > 0.9). Strong negative selection had been underway in the CNV-genes as the ones that were located entirely within the loss CNVRs appeared to be evolving rapidly as determined by the median dN plus dS values. Non-CNV genes tended to be miRNA target than CNV-genes. Furthermore, CNV-miRNAs tended to target more genes compared to non-CNV-miRNAs, and a combination of two CNV-miRNAs preferentially synergistically regulated the same target genes. We also focused our efforts on examining CNV genes and CNV-miRNAs functions, which were also involved in the lipid metabolism, including DGAT1, DGAT2, MOGAT2, miR143, miR335, and miRLET7. Further molecular experiments and independent large studies are needed to confirm our findings.

scholarly journals A prenatal diagnosis and genetics study of five pedigrees in the Chinese population with Xp22.31 microduplication

2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Jianlong Zhuang ◽  
Yuanbai Wang ◽  
Shuhong Zeng ◽  
Chunling Lv ◽  
Yiming Lin ◽  
...  
Keyword(s):  
High Risk ◽  
Copy Number ◽  
Chinese Population ◽  
Phenotypic Diversity ◽  
Copy Number Variants ◽  
Snp Array ◽  
Copy Number Variations ◽  
Serological Screening ◽  
X Chromosomes ◽  
Human Phenotype

Abstract Background Copy number variations (CNVs) can contribute to human phenotype, phenotypic diversity and disease susceptibility, while others may benign. In the current study, an attempt to investigate the pathogenicity of CNVs in chromosome Xp22.31 was explored. Methods G-banding and SNP-array techniques were used to analyze chromosome karyotypes and CNVs in fetuses. Parents associate with five different pedigrees possessing high risk factors in pregnancy were considered with such parameters as advanced age, high risk of serological screening and ultrasound abnormalities. Results The fetuses’ amniotic fluid karyotypes were 46, XX and those of their parents with the five pedigrees revealed no abnormalities. Here, we noticed a series of individuals with Xp22.31 duplications ranging from 534.6 kb to 1.6 Mb. It was detected through SNP array that the fetuses in Pedigree 1 and 2 had ~ 600 kb duplications in the Xp22.31 region of their X chromosomes which contained two OMIM genes, HDHD1 (OMIM: 306480) and part of STS (OMIM: 300747). The fetuses of Pedigrees 3, 4 and 5 had 1.6 Mb duplication in the same chromosome which contained four OMIM genes: HDHD1 (OMIM: 306480), STS (OMIM: 300747), PNPLA4 (OMIM: 300102) and VCX (OMIM: 300229). The duplications in the fetuses of Pedigrees 1 and 5 were inherited from the non-phenotypic parents. Pedigrees 3 and 4 refused to perform parental verification. Finally, four of the five pedigrees continue towards pregnancy with no abnormalities being observed during followed-ups. Conclusion Our study first showed duplications of Xp22.31 in Chinese population. Clinical and genetic investigation on five different pedigrees, we consider the duplication of these fragments as likely benign copy number variants (CNVs). We suggest that the duplications of Xp22.31 with recurrent duplication as a benign CNVs .

scholarly journals Natural history and genetic study of LAMA2-related muscular dystrophy in a large Chinese cohort

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Dandan Tan ◽  
Lin Ge ◽  
Yanbin Fan ◽  
Xingzhi Chang ◽  
Shuang Wang ◽  
...  
Keyword(s):  
Muscular Dystrophy ◽  
Natural History ◽  
Copy Number ◽  
Congenital Muscular Dystrophy ◽  
Severe Pneumonia ◽  
Copy Number Variations ◽  
Chinese Patients ◽  
Rapid Progression ◽  
Mild Phenotype ◽  
Pathogenic Variants

Abstract Background LAMA2-related muscular dystrophy including LAMA2-related congenital muscular dystrophy (LAMA2-CMD) and autosomal recessive limb-girdle muscular dystrophy-23 (LGMDR23) is caused by LAMA2 pathogenic variants. We aimed to describe the natural history and establish genotype–phenotype correlations in a large cohort of Chinese patients with LAMA2-related muscular dystrophy. Methods Clinical and genetic data of LAMA2-related muscular dystrophy patients enrolled from ten research centers between January 2003 and March 2021 were collected and analyzed. Results One hundred and thirty patients (116 LAMA2-CMD and 14 LGMDR23) were included. LAMA2-CMD group had earlier onset than LGMDR23 group. Head control, independent sitting and ambulation were achieved in 76.3%, 92.6% and 18.4% of LAMA2-CMD patients at median ages of 6.0 months (range 2.0–36.0 months), 11.0 months (range 6.0–36.0 months), and 27.0 months (range 18.0–84.0 months), respectively. All LGMDR23 patients achieved independent ambulation at median age of 18.0 months (range 13.0–20.0 months). Motor regression in LAMA2-CMD mainly occurred concurrently with rapid progression of contractures during 6–9 years old. Twenty-four LAMA2-related muscular dystrophy patients died, mostly due to severe pneumonia. Seizures occurred in 35.7% of LGMDR23 and 9.5% of LAMA2-CMD patients. Forty-six novel and 97 known LAMA2 disease-causing variants were identified. The top three high-frequency disease-causing variants in Han Chinese patients were c.7147C > T (p.R2383*), exon 4 deletion, and c.5156_5159del (p.K1719Rfs*5). In LAMA2-CMD, splicing variants tended to be associated with a relatively mild phenotype. Nonsense variants were more frequent in LAMA2-CMD (56.9%, 66/116) than in LGMDR23 (21.4%, 3/14), while missense disease-causing variants were more frequent in LGMDR23 (71.4%, 10/14) than in LAMA2-CMD (12.9%, 15/116). Copy number variations were identified in 26.4% of survivors and 50.0% of nonsurvivors, suggesting that copy number variations were associated with lower rate of survival (p = 0.029). Conclusions This study provides better understandings of natural history and genotype–phenotype correlations in LAMA2-related muscular dystrophy, and supports therapeutic targets for future researches.

scholarly journals Copy Number Variations of KLF6 Modulate Gene Transcription and Growth Traits in Chinese Datong Yak (Bos Grunniens)

Animals ◽  
2018 ◽  
Vol 8 (9) ◽  
pp. 145 ◽  
Author(s):  
Habtamu Goshu ◽  
Xiaoyun Wu ◽  
Min Chu ◽  
Pengjia Bao ◽  
Xuezhi Ding ◽  
...  
Keyword(s):  
Gene Expression ◽  
Copy Number ◽  
Muscle Development ◽  
Growth Traits ◽  
Gene Dosage ◽  
Phenotypic Diversity ◽  
Copy Number Variations ◽  
Real Time Quantitative Pcr ◽  
Genomic Markers ◽  
Differentiation And Proliferation

Copy number variation (CNV) is a significant marker of the genetic and phenotypic diversity among individuals that accounts for complex quantitative traits of phenotype and diseases via modulating gene dosage and disrupting coding regions in the genome. Biochemically, Kruppel-like factor 6 (KLF6) genes plays a significant role in the regulation of cell differentiation and proliferation and muscle development. The aim of this study was to detect the distributions of KLF6 copy number variations (CNVs) in five breeds of domestic yak and to explore their effect on growth traits and gene expression. The data were analyzed by real-time quantitative PCR (qPCR). Our results elucidated that a decreased CNV in the KLF6 gene is more highly associated (p < 0.05) with various growth traits than increased or normal CNVs in six-month-old and five-year-old Datong yak. Nevertheless, negative correlations between the DNA copy number and KLF6 gene expression were observed in the skeletal muscle of adult Datong yak. These results suggest that CNVs of the KLF6 gene could be crucial genomic markers for growth phenotypes of Chinese Datong yak breeds and this finding constitutes the first evidence of the biological role of KLF6 CNVs in Chinese Datong yak breeds.

Familial facioscapulohumeral muscular dystrophy: phenotypic diversity and genetic abnormality

2009 ◽  
Vol 93 (2-3) ◽  
pp. 189-192 ◽  
Author(s):  
M. Nakagawa ◽  
I. Higuchi ◽  
H. Yoshidome ◽  
Y. Isashiki ◽  
R. Ohkubo ◽  
...  
Keyword(s):  
Muscular Dystrophy ◽  
Phenotypic Diversity ◽  
Facioscapulohumeral Muscular Dystrophy ◽  
Genetic Abnormality

scholarly journals Genome-wide assessment characteristics of genes overlapping copy number variation regions in Duroc purebred population

2020 ◽  
Author(s):  
Zhipeng Wang ◽  
Yuanyuan Guo ◽  
Tao Wang ◽  
Chaoxin Zhang ◽  
Shengwei Liu ◽  
...  
Keyword(s):  
Copy Number ◽  
Target Genes ◽  
Phenotypic Diversity ◽  
Gene List ◽  
Copy Number Variations ◽  
Structural Variations ◽  
Density Region ◽  
Protein Coding ◽  
Protein Coding Genes ◽  
Strong Negative Selection

Abstract Background: Copy number variations (CNVs) are important structural variations that can cause significant phenotypic diversity. Reliable CNVs mapping can be achieved by identification of CNVs from different genetic backgrounds. Investigations on the characteristics of overlapping CNV regions (CNVRs) between protein-coding genes (CNV genes) and miRNAs (CNV-miRNAs) can reveal the potential mechanisms of their regulation. Results: In this study, we used 55K SNP arrays to detect CNVs in Duroc purebred pig. A total number of 211 CNVRs were detected with a total length of 118.48 Mb, accounting for 5.23% of the autosomal genome sequence. Of these CNVRs, 32 were gains, 175 losses, and 4 contained both types (loss and gain within the same region). The CNVRs we detected were non-randomly distributed in the swine genome and were significantly enriched in the segmental duplication and gene density region. Additionally, these CNVRs were overlapping with 1096 protein-coding genes, and 39 miRNAs, respectively. The CNV genes were enriched in terms of dosage-sensitive gene list. The expression of the CNV genes was significantly higher than that of the non-CNV genes in the adult Duroc liver and prostate. Of all detected CNV genes, 252 genes, which accounted for 22.99%, were tissue-specific (TSI > 0.9). Strong negative selection had been underway in the CNV genes as the ones that were located entirely within the loss CNVRs appeared to be evolving rapidly as determined by the median dN plus dS values. Non-CNV genes tended to be miRNA target than CNV genes. Furthermore, CNV-miRNAs tended to target more genes compared to non-CNV-miRNAs, and a combination of two CNV-miRNAs preferentially synergistically regulated the same target genes. We also focused our efforts on examining CNV genes and CNV-miRNAs, which were also involved in the lipid metabolism, including DGAT1, DGAT2, MOGAT2, miR143, miR335, and miRLET7. Conclusions: Our analyses of CNV-genes and CNV-miRNAs provide new insights into the characteristics of CNVRs in Duroc purebred population. Further molecular experiments and independent large studies are needed to confirm our findings.

FSHD: copy number variations on the theme of muscular dystrophy

2010 ◽  
Vol 207 (13) ◽  
pp. i38-i38
Author(s):  
Daphne Selvaggia Cabianca ◽  
Davide Gabellini
Keyword(s):  
Muscular Dystrophy ◽  
Copy Number ◽  
Copy Number Variations

A 39-Year-Old Man with Low Back Pain and Scapular Winging

2016 ◽  
Author(s):  
Jeffrey A. Cohen ◽  
Justin J. Mowchun ◽  
Victoria H. Lawson ◽  
Nathaniel M. Robbins
Keyword(s):  
Creatine Kinase ◽  
Low Back Pain ◽  
Muscular Dystrophy ◽  
Facioscapulohumeral Muscular Dystrophy ◽  
Low Back ◽  
Facial Weakness ◽  
The Third ◽  
D4z4 Repeat ◽  
Scapular Winging ◽  
Severity Of The Disease

Facioscapulohumeral muscular dystrophy (FSHD) is the third most common muscular dystrophy, following Duchenne muscular dystrophy and myotonic dystrophy. The clinical secerity is extremely variable, with symptom onset anywhere from infancy to middle adulthood. The cardinal clinical features of facioscapulohumeral muscular dystrophy include facial weakness and scapular winging. Other important examination findings including scalloping of the trapezius, “Popeye” forearms, horizontal axillary folds, and a positive Beevor’s sign. It can rarely present as a pattern of weakness mimicking limb-girdle muscular dystrophy with approximately 20% of patients eventually requiring a wheelchair for ambulation. Creatine kinase is normal or mildly elevated. Genetic testing for the D4Z4 repeat contraction on chromosome 4q35 detects 95% of cases but may not reflect severity of the disease.

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