Uniparental disomy: can SNP array data be used for diagnosis?

Tucker, Tracy; Schlade-Bartusiak, Kamilla; Eydoux, Patrice; Nelson, Tanya N.; Brown, Lindsay

doi:10.1038/gim.2012.35

Cited by 28 publications

(23 citation statements)

References 8 publications

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“…ROH on chromosome 15 may be due to an imprinting disorder: of 15 cases with ROH of chromosome 15, six (40%) were diagnosed with PWS [Wang et al, 2015]. Our results are consistent with previous reports of large-scale SNP array studies that described 6/15 (40%; Wang et al [2015]) patients and 7/11 (63%; Tucker et al [2012]) patients with UPD identified by SNP array having ROH for chromosome 15 [Fridman and Koiffmann, 2000].…”

Section: Discussionsupporting

confidence: 83%

“…χ 2 analysis with Fisher exact test due to the small sample size was used to compare our rate for detecting UPD by SNP microarray (ROH in 7/12 patients with UPD PWS) to the published detection rate (ROH in 7/11 with UPD15 and in 9/13 with UPD of any chromosome), and it did not differ ( p = 1.000) [Tucker et al, 2012] ( Table 2 ).…”

Section: Resultsmentioning

confidence: 99%

“…We sought to determine if SNP microarray could accurately detect ROH in patients with PWS due to UPD. In the absence of other explanations, the presence of ROH is suggestive of UPD: of 11 patients with UPD 15, seven (64%) had detectable ROH by microarray [Tucker et al, 2012]. ROH on chromosome 15 may be due to an imprinting disorder: of 15 cases with ROH of chromosome 15, six (40%) were diagnosed with PWS [Wang et al, 2015].…”

Section: Discussionmentioning

confidence: 99%

“…For microsatellite UPD assessment, polymorphic genetic markers on chromosome 15 (D15S1035, D15S128, D15S122, GABRB3, and D15S822) were amplified from genomic DNA isolated from peripheral blood samples with separation and sizing of the fluorescently labeled PCR products by capillary electrophoresis. Statistical analysis included frequency calculations and χ 2 analysis with Fisher exact test due to the small sample size to compare frequencies to published rates [Tucker et al, 2012]. …”

Section: Methodsmentioning

confidence: 99%

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Assessing the Clinical Utility of SNP Microarray for Prader-Willi Syndrome due to Uniparental Disomy

Santoro¹,

Hashimoto

McKinney

et al. 2017

Cytogenet Genome Res

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Maternal uniparental disomy (UPD) 15 is one of the molecular causes of Prader-Willi syndrome (PWS), a multisystem disorder which presents with neonatal hypotonia and feeding difficulty. Current diagnostic algorithms differ regarding the use of SNP microarray to detect PWS. We retrospectively examined the frequency with which SNP microarray could identify regions of homozygosity (ROH) in patients with PWS. We determined that 7/12 (58%) patients with previously confirmed PWS by methylation analysis and microsatellite-positive UPD studies had ROH (>10 Mb) by SNP microarray. Additional assessment of 5,000 clinical microarrays, performed from 2013 to present, determined that only a single case of ROH for chromosome 15 was not caused by an imprinting disorder or identity by descent. We observed that ROH for chromosome 15 is rarely incidental and strongly associated with hypotonic infants having features of PWS. Although UPD microsatellite studies remain essential to definitively establish the presence of UPD, SNP microarray has important utility in the timely diagnostic algorithm for PWS.

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Section: Discussionsupporting

confidence: 83%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Assessing the Clinical Utility of SNP Microarray for Prader-Willi Syndrome due to Uniparental Disomy

Santoro¹,

Hashimoto

McKinney

et al. 2017

Cytogenet Genome Res

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“…However, when SNP arrays gives a normal result, it does not exclude the possibility of UPD since complete heterodisomy cannot be detected by SNP arrays. If there is a strong suspicion to UPD, a methylation test can be performed 10 .…”

Section: Snp Array In Detecting Updmentioning

confidence: 99%

SNPs ANALYSIS AS A TOOL IN MOLECULAR GENETICS DIAGNOSTICS

Rusnita¹

2015

MKA

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AbstrakSingle Nucleotide Polymorphism (SNP) merupakan variasi genetik yang ditemukan pada lebih dari 1% populasi. Haplotipe, yang merupakan sekelompok SNP atau alel dalam satu kromosom, dapat di turunkan ke generasi selanjutnya dan dapat digunakan untuk menelusuri gen penyebab penyakit (marker genetik). Artikel ini bertujuan menjelaskan aplikasi analisis SNP dalam diagnosis beberapa sindrom yang disebabkan gangguan genetik. Berdasarkan laporan studi terdahulu, sindrom yang disebabkan oleh UPD (uniparental disomy) maupun penyakit autosomal resesif yang muncul sebagai akibat perkawinan sedarah dapat dideteksi dengan SNP array melalui analisis block of homozygosity dalam kromosom. Kelebihan lain SNP array adalah kemampuannya dalam mendeteksi mosaicism level rendah yang tidak terdeteksi dengan pemeriksaan sitogenetik konvensional. Bahkan saat ini, SNP array sedang diujicobakan dalam IVF untuk mendapatkan bayi yang sehat. Hal ini dapat dilakukan dengan mendeteksi ada atau tidaknya gen tunggal penyebab penyakit pada embrio hasil bayi tabung sebelum embrio ditanamkan ke uterus. Analisis SNP dengan SNP array mempunyai banyak kelebihan dibanding metode pemeriksaan SNP lainnya dan diharapkan dapat digunakan secara luas dalam bidang diagnostik molekuler genetik di masa mendatang. Kata kunci: SNP, SNP array, block of homozygosity, diagnostik, penyakit autosomal resesif AbstractSingle Nucleotide Polymorphism (SNP) is a genetic variant with a frequency of >1% of a large population. Haplotypes, a combination of a set of SNPs/alleles that appear as "associated blocks" on one chromosome, tend to be inherited together to the next offspring and can be used as genetic markers to trace particular diseases. This article aimed at explaining of SNP analysis application in diagnosis of genetic-disorder related syndrome. Previous studies showed that syndromes caused by UPD or autosomal recessive disorder as a result of consanguineous marriage can be identified by SNP array through analysing block of homozygosity region in a chromosome. Another advantage of SNP arrays is its ability in detecting low level mosaicism which was unidentified by conventional cytogenetic examination. Nowadays, SNP arrays are included in IVF process to obtain a healthy baby. It can be done by detecting the absence or the presence of disease-causing single gene in an embryo before it implanted to the womb. SNP analysis with SNP array has many advantages over other SNP analysis methods and is therefore expected can be widely used in the future in the field of molecular diagnostic.

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Variable approaches to genetic counseling for microarray regions of homozygosity associated with parental relatedness

Grote

Myers

Lovell

et al. 2013

American J of Med Genetics Pt A

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SNP microarrays are capable of detecting regions of homozygosity (ROH) which can suggest parental relatedness. This study was designed to describe pre- and post-test counseling practices of genetics professionals regarding ROH, explore perceived comfort and ethical concerns in the follow-up of such results, demonstrate awareness of laws surrounding duty to report consanguinity and incest, and allow respondents to share their personal experiences with results suggesting a parental relationship. A 35 question survey was administered to 240 genetic counselors and geneticists who had ordered or counseled for SNP microarray. The results are presented using descriptive statistics. There was variation in both pre- and post-test counseling practices of genetics professionals. Twenty-five percent of respondents reported pre-test counseling that ROH can indicate parental relatedness. The most commonly reported ethical concern was disclosure of findings suggesting parental relatedness to parents of the patient; only 48.4% reported disclosing parental relatedness when indicated. Fifty-seven percent felt comfortable receiving results suggesting parental consanguinity while 17% felt comfortable receiving results suggesting parental incest. Twenty percent of respondents were extremely/moderately familiar with the laws about duty to report incest. Personal experiences in post-test counseling included both parental acknowledgement and denial of relatedness. This study highlights the differences in genetics professionals' pre- and post-test counseling practices, comfort, and experiences surrounding parental relatedness suggested by SNP microarray results. It identifies a need for professional organizations to offer guidance to genetics professionals about how to respond to and counsel for molecular results suggesting parental consanguinity or incest.

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Uniparental disomy: can SNP array data be used for diagnosis?

Cited by 28 publications

References 8 publications

Assessing the Clinical Utility of SNP Microarray for Prader-Willi Syndrome due to Uniparental Disomy

Assessing the Clinical Utility of SNP Microarray for Prader-Willi Syndrome due to Uniparental Disomy

SNPs ANALYSIS AS A TOOL IN MOLECULAR GENETICS DIAGNOSTICS

Variable approaches to genetic counseling for microarray regions of homozygosity associated with parental relatedness

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