scholarly journals Copy neutral absence of heterozygosity on chromosome 15 distal long arm: A surrogate marker for Prader–Willi/Angelman syndromes?

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Veronica Ortega ◽  
Raymond J. Louie ◽  
Melanie A. Jones ◽  
Alka Chaubey ◽  
Barbara R. DuPont ◽  
...  
Keyword(s):  
Uniparental Disomy ◽  
Surrogate Marker ◽  
Chromosome Analysis ◽  
Paternal Allele ◽  
Noxious Stimulation ◽  
Chromosome 15 ◽  
Single Nucleotide ◽  
Single Chromosome ◽  
Specific Pcr ◽  
Oral Skills

Abstract Background Copy-neutral absence of heterozygosity (CN-AOH) observed on a single chromosome or part of a chromosome may be indicative of uniparental disomy (UPD) and may require additional testing when such chromosomes or chromosome regions are known to harbor imprinted genes. Case presentation Here we report 2 cases of neonates that presented to clinic with hypotonia, poor oral skills including inability to feed by mouth, weak cry, no response to noxious stimulation and vertical plantar creases (case 1) and hypotonia and respiratory distress (case 2). A preliminary chromosome analysis showed normal karyotypes in both cases while the high-resolution single nucleotide polymorphism (SNP) microarray showed copy neutral absence of heterozygosity involving chromosome 15 distal long arm. In case 1, the CN-AOH involved a 28.7 Mb block from genomic coordinates 73703619_102429049. In case 2, the CN-AOH involved a 15.3 Mb block from genomic coordinates 54729197_70057534. In both cases, methylation-specific PCR did not detect an unmethylated allele for the SNRPN gene suggesting either a deletion of paternal allele or maternal UPD for chromosome 15. Since microarray analysis did not show any copy number alterations on chromosome 15, a microdeletion was ruled out. Conclusions Based on our cases, we suggest that CN-AOH on chromosome 15, even if it does not involve the critical region of 15q12q13, should warrant additional studies for diagnosis of Prader–Willi/Angelman syndromes.

scholarly journals Quantitative Analysis of SRNPN Gene Methylation by Pyrosequencing as a Diagnostic Test for Prader–Willi Syndrome and Angelman Syndrome

2006 ◽  
Vol 52 (6) ◽  
pp. 1005-1013 ◽  
Author(s):  
Helen E White ◽  
Victoria J Durston ◽  
John F Harvey ◽  
Nicholas CP Cross
Keyword(s):  
Diagnostic Test ◽  
Angelman Syndrome ◽  
Uniparental Disomy ◽  
Chromosome 15 ◽  
Prader Willi Syndrome ◽  
Maternal Uniparental Disomy ◽  
Cpg Sites ◽  
Specific Pcr ◽  
Small Nuclear Ribonucleoprotein ◽  
Maternal Contribution

Abstract Background: Angelman syndrome (AS) and Prader–Willi syndrome (PWS) are 2 distinct neurodevelopmental disorders caused primarily by deficiency of specific parental contributions at an imprinted domain within the chromosomal region 15q11.2-13. In most cases, lack of paternal contribution leads to PWS either by paternal deletion (∼70%) or maternal uniparental disomy (UPD; ∼30%). Most cases of AS result from the lack of a maternal contribution from this same region by maternal deletion (∼70%) or by paternal UPD (∼5%). Analysis of allelic methylation differences at the small nuclear ribonucleoprotein polypeptide N (SNRPN) locus can differentiate the maternally and paternally inherited chromosome 15 and can be used as a diagnostic test for AS and PWS. Methods: Sodium bisulfite–treated genomic DNA was PCR-amplified for the SNRPN gene. We used pyrosequencing to individually quantify the resulting artificial C/T sequence variation at CpG sites. Anonymized DNA samples from PWS patients (n = 40), AS patients (n = 31), and controls (n = 81) were analyzed in a blinded fashion with 2 PCR and 3 pyrosequencing reactions. We compared results from the pyrosequencing assays with those obtained with a commonly used methylation-specific PCR (MS-PCR) diagnostic protocol. Results: The pyrosequencing assays had a sensitivity and specificity of 100% and provided quantification of methylation at 12 CpG sites within the SNRPN locus. The resulting diagnoses were 100% concordant with those obtained from the MS-PCR protocol. Conclusions: Pyrosequencing is a rapid and robust method for quantitative methylation analysis of the SNRPN locus and can be used as a diagnostic test for PWS and AS.

Loss of Heterozygosity on the Distal Long Arm of Chromosome 15: An Allusion for Prader-willi Syndromes?

2021 ◽  
Author(s):  
Yang-Li Dai ◽  
Ke Huang ◽  
Ming-Qiang Zhu ◽  
Mian-Ling Zhong ◽  
Guan-Ping Dong ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Loss Of Heterozygosity ◽  
Critical Region ◽  
Neutral Loss ◽  
Neurodevelopmental Disorder ◽  
Uniparental Disomy ◽  
Chromosome 15 ◽  
Maternal Uniparental Disomy ◽  
Specific Pcr ◽  
Dependent Probe

Abstract BackgroundPrader-Willi syndrome (PWS) is a rare neurodevelopmental disorder that is partially caused by maternal uniparental disomy (UPD) of chromosome 15. Copy-neutral loss of heterozygosity (CN-LOH) observed on the distal long arm of chromosome 15 may be an indicator of UPD and may require additional genetic testing as chromosome 15 is known to harbor imprinted genes.MethodsChromosome microarray (CMA) was performed for two children with developmental disabilities or congenital anomalies. The results showed CN-LOH on the distal long arm of chromosome 15. Thereafter, methylation-specific PCR (MS-PCR) or methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) was performed to confirm the diagnosis of PWS.ResultsMS-PCR did not detect an unmethylated allele for the SNRPN gene or MS-MLPA hypermethylation in 15q11.2-q13.1 region, supporting the diagnosis of PWS.ConclusionsThese data suggested that LOH on chromosome 15, and even the critical region of 15q11.2q13.1 was not involved, perhaps due to partial heterodisomy and partial isodisomy UPD15. Hence, other genetic tests are warranted for the diagnosis of PWS.

Analysis of Inter-Chromosomal Distribution of Disease-Related Genes in Human Genome

2020 ◽  
Vol 21 (11) ◽  
pp. 1068-1077
Author(s):  
Xiaochao Sun ◽  
Bin Yang ◽  
Qunye Zhang
Keyword(s):  
Spatial Distribution ◽  
Model Organisms ◽  
Nucleotide Polymorphisms ◽  
Chromosomal Distribution ◽  
Single Nucleotide ◽  
Protein Coding ◽  
Single Chromosome ◽  
Deletion Mutations ◽  
Protein Coding Genes ◽  
Disease Related Genes

: Many studies have shown that the spatial distribution of genes within a single chromosome exhibits distinct patterns. However, little is known about the characteristics of inter-chromosomal distribution of genes (including protein-coding genes, processed transcripts and pseudogenes) in different genomes. In this study, we explored these issues using the available genomic data of both human and model organisms. Moreover, we also analyzed the distribution pattern of protein-coding genes that have been associated with 14 common diseases and the insert/deletion mutations and single nucleotide polymorphisms detected by whole genome sequencing in an acute promyelocyte leukemia patient. We obtained the following novel findings. Firstly, inter-chromosomal distribution of genes displays a nonstochastic pattern and the gene densities in different chromosomes are heterogeneous. This kind of heterogeneity is observed in genomes of both lower and higher species. Secondly, protein-coding genes involved in certain biological processes tend to be enriched in one or a few chromosomes. Our findings have added new insights into our understanding of the spatial distribution of genome and disease- related genes across chromosomes. These results could be useful in improving the efficiency of disease-associated gene screening studies by targeting specific chromosomes.

scholarly journals Prenatal diagnosis of 7 cases with uniparental disomy by utilization of single nucleotide polymorphism array

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Lili Zhou ◽  
Zhaoke Zheng ◽  
Yunzhi Xu ◽  
Xiaoxiao Lv ◽  
Chenyang Xu ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphism ◽  
Prenatal Diagnosis ◽  
Molecular Analysis ◽  
Correct Diagnosis ◽  
Snp Array ◽  
Uniparental Disomy ◽  
Chromosome 1 ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
Rescue Mechanism

Abstract Background The phenotypes of uniparental disomy (UPD) are variable, which may either have no clinical impact, lead to clinical signs and symptoms. Molecular analysis is essential for making a correct diagnosis. This study involved a retrospective analysis of 4512 prenatal diagnosis samples and explored the molecular characteristics and prenatal phenotypes of UPD using a single nucleotide polymorphism (SNP) array. Results Out of the 4512 samples, a total of seven cases of UPD were detected with an overall frequency of 0.16%. Among the seven cases of UPD, two cases are associated with chromosomal aberrations (2/7), four cases (4/7) had abnormal ultrasonographic findings. One case presented with iso-UPD (14), and two case presented with mixed hetero/iso-UPD (15), which were confirmed by Methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) as maternal UPD (15) associated with Prader-Willi syndrome (PWS). Four cases had iso-UPD for chromosome 1, 3, 14, and 16, respectively; this is consistent with the monosomy rescue mechanism. Another three cases presented with mixed hetero/isodisomy were consistent with a trisomy rescue mechanism. Conclusion The prenatal phenotypes of UPD are variable and molecular analysis is essential for making a correct diagnosis and genetic counselling of UPD. The SNP array is a useful genetic test in prenatal diagnosis cases with UPD.

Typing for all known HLA-DR alleles by group-specific PCR and flow cytometry-based multiplexed single nucleotide extension

2003 ◽  
Vol 64 (10) ◽  
pp. S38
Author(s):  
Yanzheng Zhang ◽  
Charlie Costin ◽  
Christopher Giang ◽  
Robert Vorhaben ◽  
Peter Stastny
Keyword(s):  
Flow Cytometry ◽  
Single Nucleotide ◽  
Specific Pcr ◽  
Hla Dr

A compendium of myeloma-associated chromosomal copy number abnormalities and their prognostic value

Blood ◽  
2010 ◽  
Vol 116 (15) ◽  
pp. e56-e65 ◽  
Author(s):  
Brian A. Walker ◽  
Paola E. Leone ◽  
Laura Chiecchio ◽  
Nicholas J. Dickens ◽  
Matthew W. Jenner ◽  
...  
Keyword(s):  
Copy Number ◽  
Uniparental Disomy ◽  
Nuclear Factor Κb ◽  
Expression Array ◽  
Single Nucleotide ◽  
Mapping Array ◽  
Prognostic Importance ◽  
Dna Copy Number Alterations ◽  
Cycle Regulation

Abstract To obtain a comprehensive genomic profile of presenting multiple myeloma cases we performed high-resolution single nucleotide polymorphism mapping array analysis in 114 samples alongside 258 samples analyzed by U133 Plus 2.0 expression array (Affymetrix). We examined DNA copy number alterations and loss of heterozygosity (LOH) to define the spectrum of minimally deleted regions in which relevant genes of interest can be found. The most frequent deletions are located at 1p (30%), 6q (33%), 8p (25%), 12p (15%), 13q (59%), 14q (39%), 16q (35%), 17p (7%), 20 (12%), and 22 (18%). In addition, copy number-neutral LOH, or uniparental disomy, was also prevalent on 1q (8%), 16q (9%), and X (20%), and was associated with regions of gain and loss. Based on fluorescence in situ hybridization and expression quartile analysis, genes of prognostic importance were found to be located at 1p (FAF1, CDKN2C), 1q (ANP32E), and 17p (TP53). In addition, we identified common homozygously deleted genes that have functions relevant to myeloma biology. Taken together, these analyses indicate that the crucial pathways in myeloma pathogenesis include the nuclear factor-κB pathway, apoptosis, cell-cycle regulation, Wnt signaling, and histone modifications. This study was registered at http://isrctn.org as ISRCTN68454111.

scholarly journals Somatic uniparental disomy with a rare EFL1 variant causes Shwachman-Diamond syndrome through dysregulating ribosomal protein synthesis

2018 ◽  
Author(s):  
Sangmoon Lee ◽  
Chang Hoon Shin ◽  
Che Ry Hong ◽  
Jun-Dae Kim ◽  
Ah-Ra Kim ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Protein Synthesis ◽  
Ribosomal Protein ◽  
Rare Variant ◽  
Translational Control ◽  
Uniparental Disomy ◽  
Chromosome 15 ◽  
East Asians ◽  
Shwachman Diamond Syndrome ◽  
Ribosomal Protein Synthesis

We present three unrelated Korean Shwachman-Diamond syndrome (SDS) patients that carry an incomplete but identical homozygous EFL1 p.Thr1069Ala variant due to a bone marrow-specific mosaic uniparental disomy (UPD) in chromosome 15. This rare variant is found in 0.017% of East Asians and is asymptomatic in a heterozygous status, but harbors a hypomorphic effect, leading to 80S assembly of ribosomal protein (RP) transcripts. We propose a novel somatically-induced pathogenesis mechanism and EFL1 dysfunction that eventually leads to aberrant translational control and ribosomopathy.

scholarly journals Genome-Wide Linkage Mapping for Preharvest Sprouting Resistance in Wheat Using 15K Single-Nucleotide Polymorphism Arrays

2021 ◽  
Vol 12 ◽  
Author(s):  
Lingli Li ◽  
Yingjun Zhang ◽  
Yong Zhang ◽  
Ming Li ◽  
Dengan Xu ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphism ◽  
Linkage Mapping ◽  
Cost Effective ◽  
Wheat Breeding ◽  
Preharvest Sprouting ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
Specific Pcr ◽  
Grain Color ◽  
Sprouting Resistance

Preharvest sprouting (PHS) significantly reduces grain yield and quality. Identification of genetic loci for PHS resistance will facilitate breeding sprouting-resistant wheat cultivars. In this study, we constructed a genetic map comprising 1,702 non-redundant markers in a recombinant inbred line (RIL) population derived from cross Yangxiaomai/Zhongyou9507 using the wheat 15K single-nucleotide polymorphism (SNP) assay. Four quantitative trait loci (QTL) for germination index (GI), a major indicator of PHS, were identified, explaining 4.6–18.5% of the phenotypic variances. Resistance alleles of Qphs.caas-3AL, Qphs.caas-3DL, and Qphs.caas-7BL were from Yangxiaomai, and Zhongyou9507 contributed a resistance allele in Qphs.caas-4AL. No epistatic effects were detected among the QTL, and combined resistance alleles significantly increased PHS resistance. Sequencing and linkage mapping showed that Qphs.caas-3AL and Qphs.caas-3DL corresponded to grain color genes Tamyb10-A and Tamyb10-D, respectively, whereas Qphs.caas-4AL and Qphs.caas-7BL were probably new QTL for PHS. We further developed cost-effective, high-throughput kompetitive allele-specific PCR (KASP) markers tightly linked to Qphs.caas-4AL and Qphs.caas-7BL and validated their association with GI in a test panel of cultivars. The resistance alleles at the Qphs.caas-4AL and Qphs.caas-7BL loci were present in 72.2 and 16.5% cultivars, respectively, suggesting that the former might be subjected to positive selection in wheat breeding. The findings provide not only genetic resources for PHS resistance but also breeding tools for marker-assisted selection.

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