Regions of homozygosity identified by SNP microarray analysis aid in the diagnosis of autosomal recessive disease and incidentally detect parental blood relationships

Sund, Kristen L.; Zimmerman, Sarah; Thomas, Cameron; Mitchell, Anna L.; Prada, Carlos E.; Grote, Lauren; Bao, Liming; Martin, Lisa J.; Smolarek, Teresa A.

doi:10.1038/gim.2012.94

Cited by 75 publications

(84 citation statements)

References 28 publications

(41 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Overestimation of total AOH due to false positives or errors in AOH size can erroneously suggest that a given sample exhibits more AOH than that in the general population. Consanguinity is not an uncommon incidental finding in SNP testing, 11,[20][21][22] and AOH findings are not typically confirmed by a second method, so there is a legitimate risk for reporting false-positive AOH results when using LD arrays. AOH results must therefore be reported with these caveats and should never be considered diagnostic for a recessive condition.…”

Section: Discussionmentioning

confidence: 99%

Density matters: comparison of array platforms for detection of copy-number variation and copy-neutral abnormalities

Mason‐Suares

Kim

Grimmett

et al. 2013

Genetics in Medicine

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 99%

Density matters: comparison of array platforms for detection of copy-number variation and copy-neutral abnormalities

Mason‐Suares

Kim

Grimmett

et al. 2013

Genetics in Medicine

View full text Add to dashboard Cite

“…The addition of single-nucleotide polymorphism (SNP) probes in microarrays has the added advantage of enabling identification of long contiguous regions of allelic homozygosity (ROH). [1][2][3] These copy neutral aberrations are either multiple across the genome and likely due to identity by descent (IBD), or due to segmental or whole chromosome uniparental disomy (UPD) when restricted to a single chromosome. The associated findings of a cytogenetic abnormality with whole chromosome uniparental disomy is well known and, in some cases, a recurrent phenomenon.…”

Section: Introductionmentioning

confidence: 99%

Concurrent triplication and uniparental isodisomy: evidence for microhomology-mediated break-induced replication model for genomic rearrangements

et al. 2014

View full text Add to dashboard Cite

Whole-genome oligonucleotide single-nucleotide polymorphism (oligo-SNP) arrays enable simultaneous interrogation of copy number variations (CNVs), copy neutral regions of homozygosity (ROH) and uniparental disomy (UPD). Structural variation in the human genome contributes significantly to genetic variation, and often has deleterious effects leading to disease causation. Co-occurrence of CNV and regions of allelic homozygosity in tandem involving the same chromosomal arm are extremely rare. Replication-based mechanisms such as microhomology-mediated break-induced replication (MMBIR) are recent models predicted to induce structural rearrangements and gene dosage aberrations; however, supportive evidence in humans for oneended DNA break repair coupled with MMBIR giving rise to interstitial copy number gains and distal loss of heterozygosity has not been documented. We report on the identification and characterization of two cases with interstitial triplication followed by uniparental isodisomy (isoUPD) for remainder of the chromosomal arm. Case 1 has a triplication at 9q21.11-q21.33 and segmental paternal isoUPD for 9q21.33-qter, and presented with citrullinemia with a homozygous mutation in the argininosuccinate synthetase gene (ASS1 at 9q34.1). Case 2 has a triplication at 22q12.1-q12.2 and segmental maternal isoUPD 22q12.2-qter, and presented with hearing loss, mild dysmorphic features and bilateral iris coloboma. Interstitial triplication coupled with distal segmental isoUPD is a novel finding that provides human evidence for one-ended DNA break and replication-mediated repair. Both copy number gains and isoUPD may contribute to the phenotype. Significantly, these cases represent the first detailed genomic analysis that provides support for a MMBIR mechanism inducing copy number gains and segmental isoUPD in tandem.

show abstract

“…1,7 Incidental detection of parental consanguinity by SNP array in children with developmental or congenital anomalies has been demonstrated in the literature. 2,8 In case 1, SNP array was performed for multiple congenital anomalies.…”

Section: Discussionmentioning

confidence: 99%

Institutional Protocol to Manage Consanguinity Detected by Genetic Testing in Pregnancy in a Minor

et al. 2015

View full text Add to dashboard Cite

Single-nucleotide polymorphism arrays and other types of genetic tests have the potential to detect first-degree consanguinity and uncover parental rape in cases of minor teenage pregnancy. We present 2 cases in which genetic testing identified parental rape of a minor teenager. In case 1, single-nucleotide polymorphism array in a patient with multiple developmental abnormalities demonstrated multiple long stretches of homozygosity, revealing parental rape of a teenage mother. In case 2, a vague maternal sexual assault history and diagnosis of Pompe disease by direct gene sequencing identified parental rape of a minor. Given the medical, legal, and ethical implications of such revelations, a protocol was developed at our institution to manage consanguinity identified via genetic testing.

show abstract

Regions of homozygosity identified by SNP microarray analysis aid in the diagnosis of autosomal recessive disease and incidentally detect parental blood relationships

Cited by 75 publications

References 28 publications

Density matters: comparison of array platforms for detection of copy-number variation and copy-neutral abnormalities

Density matters: comparison of array platforms for detection of copy-number variation and copy-neutral abnormalities

Concurrent triplication and uniparental isodisomy: evidence for microhomology-mediated break-induced replication model for genomic rearrangements

Institutional Protocol to Manage Consanguinity Detected by Genetic Testing in Pregnancy in a Minor

Contact Info

Product

Resources

About