Array‐based comparative genomic hybridization analysis of recurrent chromosome 15q rearrangements

Sahoo, Trilochan; Shaw, Chad A.; Young, Anthony P.; Whitehouse, Nathan L.; Schroer, Richard J.; Stevenson, Roger E.; Beaudet, Arthur L.

doi:10.1002/ajmg.a.31000

Cited by 43 publications

(41 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[5][6][7] However, there are rare PWS and AS patients with an atypical distal BP at BP4 or BP5. 8,9 Additionally, in a few patients, the 15q11.2-q13 region may be deleted as a result of an unbalanced translocation, which will yield unique BPs within proximal 15q. 10,11 Despite PWS being a well-characterized genetic disorder, specific genetic factors contributing to each of the distinct clinical features of PWS are not clearly understood.…”

Section: Introductionmentioning

confidence: 99%

Unique and atypical deletions in Prader–Willi syndrome reveal distinct phenotypes

et al. 2011

Self Cite

View full text Add to dashboard Cite

Prader-Willi syndrome (PWS) is a multisystem, contiguous gene disorder caused by an absence of paternally expressed genes within the 15q11.2-q13 region via one of the three main genetic mechanisms: deletion of the paternally inherited 15q11.2-q13 region, maternal uniparental disomy and imprinting defect. The deletion class is typically subdivided into Type 1 and Type 2 based on their proximal breakpoints (BP1-BP3 and BP2-BP3, respectively). Despite PWS being a well-characterized genetic disorder the role of the specific genes contributing to various aspects of the phenotype are not well understood. Methylationspecific multiplex ligation-dependent probe amplification (MS-MLPA) is a recently developed technique that detects copy number changes and aberrant DNA methylation. In this study, we initially applied MS-MLPA to elucidate the deletion subtypes of 88 subjects. In our cohort, 32 had a Type 1 and 49 had a Type 2 deletion. The remaining seven subjects had unique or atypical deletions that were either smaller (n¼5) or larger (n¼2) than typically described and were further characterized by array-based comparative genome hybridization. In two subjects both the PWS region (15q11.2) and the newly described 15q13.3 microdeletion syndrome region were deleted. The subjects with a unique or an atypical deletion revealed distinct phenotypic features. In conclusion, unique or atypical deletions were found in B8% of the deletion subjects with PWS in our cohort. These novel deletions provide further insight into the potential role of several of the genes within the 15q11.2 and the 15q13.3 regions.

show abstract

Section: Introductionmentioning

confidence: 99%

Unique and atypical deletions in Prader–Willi syndrome reveal distinct phenotypes

et al. 2011

Self Cite

View full text Add to dashboard Cite

show abstract

“…The validation of genomic clones, and production and analysis of array-CGH experiments were carried out as described previously. 8 The breakpoints defining each deletion predicted by array CGH were confirmed by FISH analysis, utilizing clones within and flanking the deletion.…”

mentioning

confidence: 99%

Identification of novel deletions of 15q11q13 in Angelman syndrome by array-CGH: molecular characterization and genotype–phenotype correlations

et al. 2007

Self Cite

View full text Add to dashboard Cite

Angelman syndrome (AS) is a neurodevelopmental disorder characterized by mental retardation, absent speech, ataxia, and a happy disposition. Deletions of the 15q11q13 region are found in approximately 70% of AS patients. The deletions are sub-classified into class I and class II based on their sizes of B6.8 and B6.0, respectively, with two different proximal breakpoints and a common distal breakpoint. Utilizing a chromosome 15-specific comparative genomic hybridization genomic microarray (array-CGH), we have identified, determined the deletion sizes, and mapped the breakpoints in a cohort of 44 cases, to relate those breakpoints to the genomic architecture and derive more precise genotype -phenotype correlations. Interestingly four patients of the 44 studied (9.1%) had novel and unusually large deletions, and are reported here. This is the first report of very large deletions of 15q11q13 resulting in AS; the largest deletion being 410.6 Mb. These novel deletions involve three different distal breakpoints, two of which have been earlier shown to be involved in the generation of isodicentric 15q chromosomes (idic15). Additionally, precise determination of the deletion breakpoints reveals the presence of directly oriented low-copy repeats (LCRs) flanking the recurrent and novel breakpoints. The LCRs are adequate in size, orientation, and homology to enable abnormal recombination events leading to deletions and duplications. This genomic organization provides evidence for a common mechanism for the generation of both common and rare deletion types. Larger deletions result in a loss of several genes outside the common Angelman syndrome-Prader -Willi syndrome (AS -PWS) critical interval, and a more severe phenotype.

show abstract

“…Additionally, we present analyses of two PWS patients with atypical interstitial deletions of 15q. To date, recombination between LCRs in 15q has been shown to associate with various BP combinations involved in each PWS deletion type, including BP1-BP3 (type I), BP2-BP3 (type II), BP1-BP4 (type III), and BP1-BP5 (type IV) among PWS patients (Christian et al, 1995;Amos-Landgraf et al, 1999;Christian et al, 1999;Roberts et al, 2002Roberts et al, , 2003, and BP1-BP2, BP2-BP4, BP3-BP4, BP4-BP5, and BP3-BP5 among patients with other neurogenetic disorders (Murthy et al, 2007;Sahoo et al, 2005;Sharp et al, 2008). We believe that the delineation of the genetic basis of PWS from different ethnic backgrounds and the precise positioning of breakpoints in recurrent and novel PWS deletion patients will have great implications on our understanding of potential ethnic differences in genomic architecture and the causal mechanisms of unique genomic rearrangement.…”

Section: Discussionmentioning

confidence: 99%

Genetic Studies of Prader-Willi Patients Provide Evidence for Conservation of Genomic Architecture in Proximal Chromosome 15q

Hou

Lin

et al. 2010

Annals of Human Genetics

View full text Add to dashboard Cite

SummaryPrader-Willi syndrome (PWS) is a neurogenetic disorder associated with recurrent genomic recombination involving low copy repeats (LCRs) located in the human chromosome 15q11-q13. Previous studies of PWS patients from Asia suggested that there is a higher incidence of deletion and lower incidence of maternal uniparental disomy (mUPD) compared to that of Western populations. In this report, we present genetic etiology of 28 PWS patients from Taiwan. Consistent with the genetic etiology findings from Western populations, the type II deletion appears to be the most common deletion subtype. Furthermore, the ratio of the two most common deletion subtypes and the ratio of the maternal heterodisomy to isodisomy cases observed from this study are in agreement with previous findings from Western populations. In addition, we identified and further mapped the deletion breakpoints in two patients with atypical deletions using array CGH (comparative genomic hybridization). Despite the relatively small numbers of patients in each subgroup, our findings suggest that the genomic architecture responsible for the recurrent recombination in PWS is conserved in Taiwanese of the Han Chinese heritage and Western populations, thereby predisposing chromosome 15q11-q13 to a similar risk of rearrangements.

show abstract

Array‐based comparative genomic hybridization analysis of recurrent chromosome 15q rearrangements

Cited by 43 publications

References 41 publications

Unique and atypical deletions in Prader–Willi syndrome reveal distinct phenotypes

Unique and atypical deletions in Prader–Willi syndrome reveal distinct phenotypes

Identification of novel deletions of 15q11q13 in Angelman syndrome by array-CGH: molecular characterization and genotype–phenotype correlations

Genetic Studies of Prader-Willi Patients Provide Evidence for Conservation of Genomic Architecture in Proximal Chromosome 15q

Contact Info

Product

Resources

About