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Population data and genetic characteristics of 12 X-STR loci using the Investigator® Argus X-12 Quality Sensor kit for the Kedayan population of Borneo in Malaysia

Hakim HM, Khan HO, Ismail SA, Lalung J, Kofi AE, Aziz MY, et al.

Int J Legal Med, 2021 Jul;135(4):1433-1435.
PMID: 33782746 DOI: 10.1007/s00414-021-02577-0

DNA profiling of X-chromosomal short tandem repeats (X-STR) has exceptional value in criminal investigations, especially for complex kinship and incest cases. In this study, Investigator® Argus X-12 Quality Sensor (QS) kits were successfully used to characterize 12 X-STR loci in 199 unrelated healthy Kedayan individuals living in Sabah and Sarawak, Malaysia. The LG1 haplogroup (DXS8378 - DXS10135 - DXS10148) has the largest HD (0.9799) as compared with all other closely linked haplotype groups examined (LG2; DXS7132-DXS10074-DXS10079, LG3; DXS10103-DXS10101-HPRTB and LG4; DXS10134-DXS7423-DXS10146). Data from statistical analysis showed that high combined of PDM, PDF, MEC_Krüger, MEC_Kishida, MEC_Desmarais, and MEC_Desmarais_duo values (0.999999994405922, 0.99999999999999, 0.999990463834938, 0.999999975914808, 0.999999975985006, and 0.999996491927194, respectively) in the Kedayan. In a two-dimensional scaling (MDS) plot and dendrogram constructed using allele frequencies at the 12 X-STR loci, Kedayan appear to be most closely related to their other Austronesian populations including the Malays and Filipinos as compared with other reference population groups. Findings from the present study thus demonstrate high genetic variability across the 12 tested X-STR loci and can be used for population studies and forensic applications.

Matched MeSH terms: Chromosomes, Human, X*
FISHing for 1p19q codel in oligodendroglioma

Kong PL, Cheah PL, Mun KS, Chiew SF, Lau TP, Koh CC, et al.

Malays J Pathol, 2020 Dec;42(3):369-376.
PMID: 33361717

Together with isocitrate dehydrogenase (IDH) mutation, co-deletion of 1p19q (1p19q codel) is a prerequisite for diagnosis of oligodendroglioma, making it imperative that histopathology laboratories introduce testing for 1p19q codel. To date there is still no consensus reference range and cut-offs that confirm deletion of 1p or 19q. We embarked on determining our reference range in 11 formalinfixed, paraffin-embedded non-neoplastic brain tissue using fluorescence in situ hybridisation (FISH) with the Vysis 1p36/1q25 and 19q13/19p13 FISH Probe Kit (Abbott Molecular Inc., USA). At same time we attempted to validate our methodology in 13 histologically-confirmed IDH-mutant oligodendrogliomas. For 1p, percentage cells with deletion (range=8-23%; mean±SD = 15.73±5.50%) and target: control (1p36:1q25) ratio (range = 0.89-0.96; mean±SD = 0.92±0.03) in non-neoplastic brain, differed significantly (p<0.000) from oligodendroglioma (percentage cells with deletion: range = 49-100%; mean±SD = 82.46±15.21%; target:control ratio range:0.50-0.76; mean±SD = 0.59±0.08). For 19q, percentage cells with deletion (range = 7-20%; mean±SD = 12.00±3.49%) and target:control (19q13/19p13) ratio (range:0.90-0.97; mean±SD = 0.94±0.02) in non-neoplastic brain also differed significantly from oligodendroglioma (percentage cells with deletion: range = 45-100%; mean±SD = 82.62±18.13%; target:control ratio range:0.50-0.78; mean±SD = 0.59±0.09). Using recommended calculation method, for diagnosis of 1p deletion, percentage of cells showing deletion should be >32-33% and/or target:control ratio <0.83. For 19q, percentage of cells showing deletion should be >22% and target:control ratio <0.88. Using these cut-offs all 13 oligodendroglioma demonstrated 1p19q codel.

Matched MeSH terms: Chromosomes, Human, Pair 1/genetics*
Fulltext Fine-Scale Mapping at 9p22.2 Identifies Candidate Causal Variants That Modify Ovarian Cancer Risk in BRCA1 and BRCA2 Mutation Carriers

Vigorito E, Kuchenbaecker KB, Beesley J, Adlard J, Agnarsson BA, Andrulis IL, et al.

PLoS One, 2016;11(7):e0158801.
PMID: 27463617 DOI: 10.1371/journal.pone.0158801

Population-based genome wide association studies have identified a locus at 9p22.2 associated with ovarian cancer risk, which also modifies ovarian cancer risk in BRCA1 and BRCA2 mutation carriers. We conducted fine-scale mapping at 9p22.2 to identify potential causal variants in BRCA1 and BRCA2 mutation carriers. Genotype data were available for 15,252 (2,462 ovarian cancer cases) BRCA1 and 8,211 (631 ovarian cancer cases) BRCA2 mutation carriers. Following genotype imputation, ovarian cancer associations were assessed for 4,873 and 5,020 SNPs in BRCA1 and BRCA 2 mutation carriers respectively, within a retrospective cohort analytical framework. In BRCA1 mutation carriers one set of eight correlated candidate causal variants for ovarian cancer risk modification was identified (top SNP rs10124837, HR: 0.73, 95%CI: 0.68 to 0.79, p-value 2× 10-16). These variants were located up to 20 kb upstream of BNC2. In BRCA2 mutation carriers one region, up to 45 kb upstream of BNC2, and containing 100 correlated SNPs was identified as candidate causal (top SNP rs62543585, HR: 0.69, 95%CI: 0.59 to 0.80, p-value 1.0 × 10-6). The candidate causal in BRCA1 mutation carriers did not include the strongest associated variant at this locus in the general population. In sum, we identified a set of candidate causal variants in a region that encompasses the BNC2 transcription start site. The ovarian cancer association at 9p22.2 may be mediated by different variants in BRCA1 mutation carriers and in the general population. Thus, potentially different mechanisms may underlie ovarian cancer risk for mutation carriers and the general population.

Matched MeSH terms: Chromosomes, Human, Pair 9*
Fulltext Trisomy X and myelodysplastic syndrome (MDS) with eosinophilia

Eusni, R.M.T., Leong, C.F., Salwa, S.

Malaysian Journal of Medicine and Health Sciences, 2012;8(2):65-67.
MyJurnal

We reported a young patient with myelodysplastic syndrome (MDS) with eosinophilia, in which her chromosomal analysis revealed the presence of trisomy X and a marker chromosome at chromosome 11. The technique used to detect the chromosomal abnormalities is a multicoloured –fluorescent in situ hybridization technique (M-FISH). Our observation suggested that these underlying chromosomal abnormalities were probably responsible for her development of MDS with eosinophilia.
Myelodysplastic syndrome (MDS) is a condition whereby there is ineffective production of haematopoietic stem cells and poor quality of cells produced. The cause can either be a primary bone marrow problem, de novo or therapy related. Most MDS cases are secondary rather than primary. Many chromosomal abnormalities have been found in cases of myelodysplastic syndrome. We described a case of MDS with eosinophilia in association with presence of trisomy X and a marker chromosome in chromosome 11.

Matched MeSH terms: Chromosomes, Human, Pair 11; Chromosomes, Human, X
Down syndrome as a result of de novo robertsonian translocation involving chromosome 14 and 21: a case report

Norhasimah, M.M., Ahmad Tarmizi, A.B., Azman, B.A., Zilfalil, B.A., Ankathil, R.

Malaysian Journal of Paediatrics and Child Health, 2007;15(1):46-49.
MyJurnal

Generally, the karyotype profile of Down Syndrome has been reported to be full trisomy 21 in 92% of patients, mosaic trisomy 21 in 4% of patients and translocation involving chromosome 21 in 4% of patients in most of the population groups worldwide. But, karyotype analysis of 149 DS patients at the Human Genome Center, USM, during the past five years revealed that free trisomy accounted for 94.6%, mosaic trisomy 21 for 4.7% and translocation involving chromosome 21 in 0.7% of the Down Syndrome etiology in North East Malaysian population, indicating a low frequency of translocation DS in this region. Here, we report one case of translocation Down Syndrome encountered during karyotype analysis of 149 DS cases. Karyotype showed a robertsonian translocation where an entire extra chromosome 21 was attached to the centromere of one of the chromosome 14, resulting in a derivative chromosome 14 with attached chromosome 21. Karyotype analysis of the parents revealed a normal 46,XY pattern for father and 46,XX pattern for mother indicating that this robertsonian translocation had arisen de novo either prior to or at conception.

Matched MeSH terms: Chromosomes, Human, Pair 14; Chromosomes, Human, Pair 21
Characterization of genetic sequence variation of 58 STR loci in four major population groups

Novroski NMM, King JL, Churchill JD, Seah LH, Budowle B

Forensic Sci Int Genet, 2016 11;25:214-226.
PMID: 27697609 DOI: 10.1016/j.fsigen.2016.09.007

Massively parallel sequencing (MPS) can identify sequence variation within short tandem repeat (STR) alleles as well as their nominal allele lengths that traditionally have been obtained by capillary electrophoresis. Using the MiSeq FGx Forensic Genomics System (Illumina), STRait Razor, and in-house excel workbooks, genetic variation was characterized within STR repeat and flanking regions of 27 autosomal, 7 X-chromosome and 24 Y-chromosome STR markers in 777 unrelated individuals from four population groups. Seven hundred and forty six autosomal, 227 X-chromosome, and 324 Y-chromosome STR alleles were identified by sequence compared with 357 autosomal, 107 X-chromosome, and 189 Y-chromosome STR alleles that were identified by length. Within the observed sequence variation, 227 autosomal, 156 X-chromosome, and 112 Y-chromosome novel alleles were identified and described. One hundred and seventy six autosomal, 123 X-chromosome, and 93 Y-chromosome sequence variants resided within STR repeat regions, and 86 autosomal, 39 X-chromosome, and 20 Y-chromosome variants were located in STR flanking regions. Three markers, D18S51, DXS10135, and DYS385a-b had 1, 4, and 1 alleles, respectively, which contained both a novel repeat region variant and a flanking sequence variant in the same nucleotide sequence. There were 50 markers that demonstrated a relative increase in diversity with the variant sequence alleles compared with those of traditional nominal length alleles. These population data illustrate the genetic variation that exists in the commonly used STR markers in the selected population samples and provide allele frequencies for statistical calculations related to STR profiling with MPS data.

Matched MeSH terms: Chromosomes, Human, X; Chromosomes, Human, Y
The trinucleotide repeat expansion on chromosome 6p (SCA1) in autosomal dominant cerebellar ataxias

Giunti P, Sweeney MG, Spadaro M, Jodice C, Novelletto A, Malaspina P, et al.

Brain, 1994 Aug;117 ( Pt 4):645-9.
PMID: 7922453

Affected members of 73 families with a variety of autosomal dominant late onset cerebellar ataxias (ADCAs) were investigated for the trinucleotide (CAG) repeat expansion which is found in pedigrees exhibiting linkage to the SCA1 locus on chromosome 6. Most of the families were too small for linkage analysis. The mutation was only found in ADCA type I, in 19 out of 38 such kindreds investigated (50%). It was slightly more common in Italian (59%) than British (50%) families, and was also found in Malaysian, Bangladeshi and Jamaican kindreds. Overall, ADCA type I patients with the expansion had a lower incidence of hyporeflexia and facial fasciculation than those without. The trinucleotide expansion was not found in eight families with ADCA and maculopathy or 24 kindreds with a pure type of ADCA, confirming that these syndromes are genetically distinct. It was also not detected in 12 patients with sporadic degenerative ataxias. DNA analysis for the SCA1 mutation is useful diagnostically in single patients or small families, and can be used for presymptomatic testing where appropriate.

Matched MeSH terms: Chromosomes, Human, Pair 6*
Fulltext Microarray-Based Genomic Analysis Identifies Germline and Somatic Copy Number Variants and Loss of Heterozygosity in Acute Myeloid Leukaemia

Ambayya, Angeli, Sasmita, Andrew Octavian, Zainina Seman, Chang, Kian Meng, Sathar, Jameela, Yegappan, Subramanian, et al.

Malaysian Journal of Medicine and Health Sciences, 2018;14(103):1-14.
MyJurnal

Insights into molecular karyotyping using comparative genomic hybridization (CGH) and single nucleotide polymorphism (SNP) arrays enable the identification of copy number variations (CNVs) at a higher resolution and facilitate the detection of copy neutral loss of heterozygosity (CN-LOH) otherwise undetectable by conventional cytogenetics. The applicability of a customised CGH+SNP 180K DNA microarray in the diagnostic evaluation of Acute Myeloid Leukaemia (AML) in comparison with conventional karyotyping was assessed in this study. Methods: Paired tumour and germline post induction (remission sample obtained from the same patient after induction) DNA were used to delineate germline variants in 41 AML samples and compared with the karyotype findings. Results: After comparing the tumour versus germline DNA, a total of 55 imbalances (n 5-10 MB = 21, n 10-20 MB = 8 and n >20 MB = 26) were identified. Gains were most common in chromosome 4 (26.7%) whereas losses were most frequent in chromosome 7 (28.6%) and X (25.0%). CN-LOH was mostly seen in chromosome 4 (75.0%). Comparison between array CGH+SNP and karyotyping revealed 20 cases were in excellent agreement and 13 cases did not concord whereas in 15 cases finding could not be confirmed as no karyotypes available. Conclusion: The use of a combined array CGH+SNP in this study enabled the detection of somatic and germline CNVs and CN-LOHs in AML. Array CGH+SNP accurately determined chromosomal breakpoints compared to conventional cytogenetics in relation to presence of CNVs and CN-LOHs.

Matched MeSH terms: Chromosomes, Human, Pair 4; Chromosomes, Human, Pair 7
Fulltext Two cases of deletion 5p syndrome: one with paternal involvement and another with atypical presentation

Azman BZ, Akhir SM, Zilfalil BA, Ankathil R

Singapore Med J, 2008 Apr;49(4):e98-e100.
PMID: 18418516

We report two cases of deletion 5p or cri du chat syndrome (CdCS) with different presentations and risks of transmission: one case with paternal chromosome 5 involvement and another, a de novo case with atypical clinical presentation. Cytogenetic analysis was performed on the two cases and their parents. GTG-banded karyotype analysis of Cases 1 and 2 revealed abnormal 46,XY,del(5)(p13-15) male karyotypes. For Case 1, the mother showed normal female karyotype while the father showed an abnormal karyotype involving a balanced translocation 46,XY,t(5;10)(p13;p15). For Case 2, however, both parents showed a normal karyotype pattern. In Case 1, the clinical features, particularly the distinct facial phenotype in combination with a characteristic cat-like cry and hypotonia, aided in the diagnosis at birth and the karyotype analysis was resolutive. The boy in Case 2 presented with atypical clinical features. Even though this patient had multiple syndromic features, the typical high pitched cat-like cry was not prominent. Instead, the patient manifested persistent stridor (from day three of life), which might have prevented the clinician from suspecting CdCS at birth. However, when this patient was presented at seven months of age for cytogenetic analysis, a confirmatory diagnosis of CdCS was established. For children with congenital abnormalities, an early clinical diagnosis confirmed through cytogenetic and molecular investigations, is important for providing personalised diagnostic and prognostic evaluation, and also for genetic counselling on the reproductive risk, particularly for patients with parental chromosome translocation involvement.

Matched MeSH terms: Chromosomes, Human, Pair 5/genetics*
Fulltext Interstitial deletion of the distal long arm of chromosome 4, del (4)(q33-q35), in association with paternal balanced translocation

Mdzin R, Ko C, Abdul Latif Z, Zakaria Z

Singapore Med J, 2008 Nov;49(11):e336-9.
PMID: 19037546

Interstitial deletions of the long arm of chromosome 4 are rare. The deletions may occur at the proximal or the distal portions of the chromosome and different breakpoints may be involved. We report an interstitial deletion of 4q: 46XY der 4 (q28;q35) in a six-year-old boy with dysmorphic features associated with moderate mental retardation. Parental chromosomal analysis showed a balanced paternal translocation.

Matched MeSH terms: Chromosomes, Human, Pair 4*
Fulltext A rare case of ambiguous genitalia

Ng SF, Boo NY, Wu LL, Shuib S

Singapore Med J, 2007 Sep;48(9):858-61.
PMID: 17728969

Genes on the Y chromosome are essential for normal sex determination and sex differentiation of male genitalia. However, genes on the X chromosome and other autosomes have been shown to be anti-testes and have a detrimental effect on this process. Addition of X chromosomes to the 46,XY karyotype results in seminiferous tubules dysgenesis, hypogonadism and malformed genitalia. We report a term male newborn with 49,XXXXY syndrome presenting with ambiguous genitalia, multiple extra-gonadal anomalies, facial dysmorphism, and radioulnar synostosis.

Matched MeSH terms: Chromosomes, Human, X/genetics*
Fulltext Molecular organization of recombinant human-Arabidopsis chromosomes in hybrid cell lines

Liu Y, Liaw YM, Teo CH, Cápal P, Wada N, Fukui K, et al.

Sci Rep, 2021 Mar 30;11(1):7160.
PMID: 33785802 DOI: 10.1038/s41598-021-86130-4

Although plants and animals are evolutionarily distant, the structure and function of their chromosomes are largely conserved. This allowed the establishment of a human-Arabidopsis hybrid cell line in which a neo-chromosome was formed by insertion of segments of Arabidopsis chromosomes into human chromosome 15. We used this unique system to investigate how the introgressed part of a plant genome was maintained in human genetic background. The analysis of the neo-chromosome in 60- and 300-day-old cell cultures by next-generation sequencing and molecular cytogenetics suggested its origin by fusion of DNA fragments of different sizes from Arabidopsis chromosomes 2, 3, 4, and 5, which were randomly intermingled rather than joined end-to-end. The neo-chromosome harbored Arabidopsis centromeric repeats and terminal human telomeres. Arabidopsis centromere wasn't found to be functional. Most of the introgressed Arabidopsis DNA was eliminated during the culture, and the Arabidopsis genome in 300-day-old culture showed significant variation in copy number as compared with the copy number variation in the 60-day-old culture. Amplified Arabidopsis centromere DNA and satellite repeats were localized at particular loci and some fragments were inserted into various positions of human chromosome. Neo-chromosome reorganization and behavior in somatic cell hybrids between the plant and animal kingdoms are discussed.

Matched MeSH terms: Chromosomes, Human, Pair 15/genetics*
Fulltext Fine mapping of chromosome 5p15.33 based on a targeted deep sequencing and high density genotyping identifies novel lung cancer susceptibility loci

Kachuri L, Amos CI, McKay JD, Johansson M, Vineis P, Bueno-de-Mesquita HB, et al.

Carcinogenesis, 2016 Jan;37(1):96-105.
PMID: 26590902 DOI: 10.1093/carcin/bgv165

Chromosome 5p15.33 has been identified as a lung cancer susceptibility locus, however the underlying causal mechanisms were not fully elucidated. Previous fine-mapping studies of this locus have relied on imputation or investigated a small number of known, common variants. This study represents a significant advance over previous research by investigating a large number of novel, rare variants, as well as their underlying mechanisms through telomere length. Variants for this fine-mapping study were identified through a targeted deep sequencing (average depth of coverage greater than 4000×) of 576 individuals. Subsequently, 4652 SNPs, including 1108 novel SNPs, were genotyped in 5164 cases and 5716 controls of European ancestry. After adjusting for known risk loci, rs2736100 and rs401681, we identified a new, independent lung cancer susceptibility variant in LPCAT1: rs139852726 (OR = 0.46, P = 4.73×10(-9)), and three new adenocarcinoma risk variants in TERT: rs61748181 (OR = 0.53, P = 2.64×10(-6)), rs112290073 (OR = 1.85, P = 1.27×10(-5)), rs138895564 (OR = 2.16, P = 2.06×10(-5); among young cases, OR = 3.77, P = 8.41×10(-4)). In addition, we found that rs139852726 (P = 1.44×10(-3)) was associated with telomere length in a sample of 922 healthy individuals. The gene-based SKAT-O analysis implicated TERT as the most relevant gene in the 5p15.33 region for adenocarcinoma (P = 7.84×10(-7)) and lung cancer (P = 2.37×10(-5)) risk. In this largest fine-mapping study to investigate a large number of rare and novel variants within 5p15.33, we identified novel lung and adenocarcinoma susceptibility loci with large effects and provided support for the role of telomere length as the potential underlying mechanism.

Matched MeSH terms: Chromosomes, Human, Pair 5*
Fulltext Evidence that breast cancer risk at the 2q35 locus is mediated through IGFBP5 regulation

Ghoussaini M, Edwards SL, Michailidou K, Nord S, Cowper-Sal Lari R, Desai K, et al.

Nat Commun, 2014 Sep 23;4:4999.
PMID: 25248036 DOI: 10.1038/ncomms5999

GWAS have identified a breast cancer susceptibility locus on 2q35. Here we report the fine mapping of this locus using data from 101,943 subjects from 50 case-control studies. We genotype 276 SNPs using the 'iCOGS' genotyping array and impute genotypes for a further 1,284 using 1000 Genomes Project data. All but two, strongly correlated SNPs (rs4442975 G/T and rs6721996 G/A) are excluded as candidate causal variants at odds against >100:1. The best functional candidate, rs4442975, is associated with oestrogen receptor positive (ER+) disease with an odds ratio (OR) in Europeans of 0.85 (95% confidence interval=0.84-0.87; P=1.7 × 10(-43)) per t-allele. This SNP flanks a transcriptional enhancer that physically interacts with the promoter of IGFBP5 (encoding insulin-like growth factor-binding protein 5) and displays allele-specific gene expression, FOXA1 binding and chromatin looping. Evidence suggests that the g-allele confers increased breast cancer susceptibility through relative downregulation of IGFBP5, a gene with known roles in breast cell biology.

Matched MeSH terms: Chromosomes, Human, Pair 2/genetics*; Chromosomes, Human, Pair 2/metabolism
Fulltext A Genome Wide Study of Copy Number Variation Associated with Nasopharyngeal Carcinoma in Malaysian Chinese Identifies CNVs at 11q14.3 and 6p21.3 as Candidate Loci

Low JS, Chin YM, Mushiroda T, Kubo M, Govindasamy GK, Pua KC, et al.

PLoS One, 2016;11(1):e0145774.
PMID: 26730743 DOI: 10.1371/journal.pone.0145774

BACKGROUND: Nasopharyngeal carcinoma (NPC) is a neoplasm of the epithelial lining of the nasopharynx. Despite various reports linking genomic variants to NPC predisposition, very few reports were done on copy number variations (CNV). CNV is an inherent structural variation that has been found to be involved in cancer predisposition.
METHODS: A discovery cohort of Malaysian Chinese descent (NPC patients, n = 140; Healthy controls, n = 256) were genotyped using Illumina® HumanOmniExpress BeadChip. PennCNV and cnvPartition calling algorithms were applied for CNV calling. Taqman CNV assays and digital PCR were used to validate CNV calls and replicate candidate copy number variant region (CNVR) associations in a follow-up Malaysian Chinese (NPC cases, n = 465; and Healthy controls, n = 677) and Malay cohort (NPC cases, n = 114; Healthy controls, n = 124).
RESULTS: Six putative CNVRs overlapping GRM5, MICA/HCP5/HCG26, LILRB3/LILRA6, DPY19L2, RNase3/RNase2 and GOLPH3 genes were jointly identified by PennCNV and cnvPartition. CNVs overlapping GRM5 and MICA/HCP5/HCG26 were subjected to further validation by Taqman CNV assays and digital PCR. Combined analysis in Malaysian Chinese cohort revealed a strong association at CNVR on chromosome 11q14.3 (Pcombined = 1.54x10-5; odds ratio (OR) = 7.27; 95% CI = 2.96-17.88) overlapping GRM5 and a suggestive association at CNVR on chromosome 6p21.3 (Pcombined = 1.29x10-3; OR = 4.21; 95% CI = 1.75-10.11) overlapping MICA/HCP5/HCG26 genes.
CONCLUSION: Our results demonstrated the association of CNVs towards NPC susceptibility, implicating a possible role of CNVs in NPC development.

Matched MeSH terms: Chromosomes, Human, Pair 11/genetics*; Chromosomes, Human, Pair 6/genetics*
The pattern and frequency of t(14;18) translocation and immunophenotype in Asian follicular lymphoma

Peh SC, Shaminie J, Tai YC, Tan J, Gan SS

Histopathology, 2004 Nov;45(5):501-10.
PMID: 15500654

Follicular lymphoma is frequently associated with t(14;18)(q32;q21) translocation. This study was undertaken to determine the pattern of Bcl-2, CD10 and Bcl-6 expression in relation to t(14;18) translocation in follicular lymphoma from a cohort of a multi-ethnic Asian population.

Matched MeSH terms: Chromosomes, Human, Pair 14*; Chromosomes, Human, Pair 18*
FISH versus real-time quantitative PCR for monitoring of minimal residual disease in chronic myeloid leukaemia patients on tyrosine kinase inhibitor therapy

Haidary AM, Azma RZ, Ithnin A, Alauddin H, Tumian NR, Tamil AM, et al.

Malays J Pathol, 2019 Aug;41(2):149-160.
PMID: 31427550

INTRODUCTION: BCR-ABL fusion gene, the oncogenic driver of CML, results from a translocation between short arms of chromosome 9 and 22. Monitoring of CML patients during treatment is essential, not only for tailoring the treatment but also to detect early relapse to enable timely intervention. Commonly used methods for detection of residual disease are conventional karyotyping, FISH and molecular methods. In this study, we compared FISH with QRT-PCR for detection of residual disease in CML.
MATERIALS AND METHODS: CML patients on tyrosine kinase inhibitor (TKI) therapy and on regular follow up at University Kebangsaan Malaysia Medical Center (UKMMC) were selected. A comparative study was conducted between FISH and QRT-PCR for BCR-ABL transcripts at diagnosis and during follow-up.
RESULTS: There was good correlation between FISH and QRT-PCR for BCR-ABL. At 6th month of follow-up post diagnosis, FISH had a sensitivity of 83.3% and specificity of 65.2% (k >0.339, p<0.033). At 12th month, the sensitivity of FISH was 83% and the specificity was 59.1% (k >0.286, p <0.065). Similarly, at the 24th month, FISH had a sensitivity of 100% and specificity of 68.8% (k >0.642, p<0.000).
DISCUSSION: Early achievement of major molecular response (MMR) and complete cytogenetic remission (CCyR) were reliable predictors of long-term maintenance of molecular remission.

Matched MeSH terms: Chromosomes, Human, Pair 9
Fulltext Draft genome of Paraburkholderia fungorum sequence type 868 recovered from human synovial tissues

Loong SK, Tan KK, Zulkifle NI, AbuBakar S

Data Brief, 2019 Aug;25:104159.
PMID: 31312701 DOI: 10.1016/j.dib.2019.104159

Paraburkholderia fungorum is an opportunistic bacteria infrequently associated with human infections. Here, we report the draft genome sequence of P. fungorum strain BF370, recovered from the synovial tissue of a patient in Malaysia. The P. fungorum genome contains a 8,950,957 bp chromosome with a G+C content of 61.8%. Colicin and heavy metal resistant genes were also present in the genome. Conserved sequence indels unique to P. fungorum were observed in the genome. The draft genome was deposited at the European Nucleotide Archive under the sample accession number ERS1776561 and study accession number PRJEB17921.

Matched MeSH terms: Chromosomes, Human, Pair 8
8q24 and 17q prostate cancer susceptibility loci in a multiethnic Asian cohort

Chan JY, Li H, Singh O, Mahajan A, Ramasamy S, Subramaniyan K, et al.

Urol Oncol, 2013 Nov;31(8):1553-60.
PMID: 22561070 DOI: 10.1016/j.urolonc.2012.02.009

OBJECTIVES: Recently, several genome-wide association studies have demonstrated a cumulative association of 5 polymorphic variants in chromosomes 8q24 and 17q with prostate cancer (CaP) risk in Caucasians, particularly those harboring aggressive clinicopathologic characteristics. The purpose of this study was to evaluate the influence of these variants on CaP susceptibility in Singaporean Asian men.
MATERIALS AND METHODS: We performed a case-control study in 289 Chinese CaP patients and 412 healthy subjects (144 Chinese, 134 Malays, and 134 Indians), and examined the association of the 5 single nucleotide polymorphisms (SNPs) with CaP.
RESULTS: In the healthy subjects, rs16901979 A-allele frequency was highest amongst Chinese (0.32) compared with Malays (0.13; P < 0.0001) or Indians (0.09; P < 0.0001); rs6983267 G-allele was highest in Indians (0.51) compared with Chinese (0.42; P = 0.041) or Malays (0.43; P = 0.077); whereas rs1859962 G-allele frequency was highest amongst Indians (0.56) compared with Chinese (0.40; P = 0.0002) or Malays (0.38; P < 0.0001). Individuals with the rs4430796 TT genotype were at increased CaP risk in the Chinese via a recessive model (odds ratios (OR) = 1.56, 95% CI = 1.04-2.33). Significant associations were observed for rs4430796 TT with Gleason scores of ≥ 7 (OR = 1.76, 95% CI = 1.14-2.73) and prostate-specific antigen (PSA) levels of ≥ 10 ng/ml at diagnosis (OR = 1.63, 95% CI = 1.01-2.63), as well as for rs6983267 GG with stage 3-4 CaPs (OR = 1.91, 95% CI = 1.01-3.61). A cumulative gene interaction influence on disease risk, which approximately doubled for individuals with at least 2 susceptibility genotypes, was also identified (OR = 2.18, 95% CI = 1.10-4.32).
CONCLUSIONS: This exploratory analysis suggests that the 5 genetic variants previously described may contribute to prostate cancer risk in Singaporean men.
KEYWORDS: Cancer; Ethnicity; Gleason; Pharmacogenetics; Polymorphism; Prostate

Matched MeSH terms: Chromosomes, Human, Pair 17/genetics*; Chromosomes, Human, Pair 8/genetics*
Fulltext Extensive Genetic Variation at the Sr22 Wheat Stem Rust Resistance Gene Locus in the Grasses Revealed Through Evolutionary Genomics and Functional Analyses

Md Hatta MA, Ghosh S, Athiyannan N, Richardson T, Steuernagel B, Yu G, et al.

Mol Plant Microbe Interact, 2020 Nov;33(11):1286-1298.
PMID: 32779520 DOI: 10.1094/MPMI-01-20-0018-R

In the last 20 years, severe wheat stem rust outbreaks have been recorded in Africa, Europe, and Central Asia. This previously well controlled disease, caused by the fungus Puccinia graminis f. sp. tritici, has reemerged as a major threat to wheat cultivation. The stem rust (Sr) resistance gene Sr22 encodes a nucleotide-binding and leucine-rich repeat receptor which confers resistance to the highly virulent African stem rust isolate Ug99. Here, we show that the Sr22 gene is conserved among grasses in the Triticeae and Poeae lineages. Triticeae species contain syntenic loci with single-copy orthologs of Sr22 on chromosome 7, except Hordeum vulgare, which has experienced major expansions and rearrangements at the locus. We also describe 14 Sr22 sequence variants obtained from both Triticum boeoticum and the domesticated form of this species, T. monococcum, which have been postulated to encode both functional and nonfunctional Sr22 alleles. The nucleotide sequence analysis of these alleles identified historical sequence exchange resulting from recombination or gene conversion, including breakpoints within codons, which expanded the coding potential at these positions by introduction of nonsynonymous substitutions. Three Sr22 alleles were transformed into wheat cultivar Fielder and two postulated resistant alleles from Schomburgk (hexaploid wheat introgressed with T. boeoticum segment carrying Sr22) and T. monococcum accession PI190945, respectively, conferred resistance to P. graminis f. sp. tritici race TTKSK, thereby unequivocally confirming Sr22 effectiveness against Ug99. The third allele from accession PI573523, previously believed to confer susceptibility, was confirmed as nonfunctional against Australian P. graminis f. sp. tritici race 98-1,2,3,5,6.[Formula: see text] Copyright © 2020 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

Matched MeSH terms: Chromosomes, Human, Pair 7

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