Whole genome mapping and identification of single nucleotide polymorphisms of four Bangladeshi individuals and their functional significance.

OBJECTIVE: The major objective of the study was to sequence the whole genome of four Bangladeshi individuals and identify variants that are known to be associated with functional changes or disease states. We also carried out an ontology analysis to identify the functions and pathways most likely to be affected by these variants. RESULTS: We identified around 900,000 common variants and close to 5 million unique ones in all four of the individuals. This included over 11,500 variants that caused nonsynonymous changes in proteins. Heart function associated pathways were heavily implicated by the ontology analysis; corroborating previous studies that claimed the Bangladeshi population as highly susceptible to heart disorders. Two variants were found that have been previously identified as pathogenic factors in familial hypercholesteremia and structural disorders of the heart. Other pathogenic variants we found were associated with pseudoxanthoma elasticum, cancer progression, polyagglutinable erythrocyte syndrome, preeclampsia, and others.

Identification of Mutation in Exon11 of BRCA1 Gene in Bangladeshi Patients with Breast Cancer.

BACKGROUND: Worldwide, breast cancer is the leading cause of cancer death in female, in Bangladesh breast cancer is the second leading cancer in both sexes, and in women it occupied the top position. Highly penetrant mutations in BRCA1 gene constitute high risk of breast cancer. The spectrum of BRCA1 gene mutations varies in different population. The objective of this study was to identify mutation in exon11 of BRCA1 gene in Bangladeshi breast cancer patients. METHODS: Genomic DNA was extracted from the histopathologically diagnosed formalin fixed paraffin embedded (FFPE) breast cancer tissues of 65 adult female patients. Two regions of exon11 of the BRCA1 gene were amplified and the amplicons were sequenced using Sanger sequencing. The sequenced nucleotides were analyzed and blast using NCBI nucleoblast. Selected demographic, reproductive and medical histories were collected and analyzed using SPSS version 20. RESULTS: The mean age of the patients was 46 years and the mean age at diagnosis was 44.64 years. The patients were married and had 2.65 ± 1.22 children except one was nulliparous, the mean age of menarche was 12.67 years. All patients had children, breastfed the babies for an average 1.5 years. Only 13.6% of the patients had hypertension and the rest had no comorbidity. The family history for cancer (breast and other cancer) was negative. Three novel mutations were found in a patient. Two among the three mutant sequences had effect on amino acid coding (DNA sequence change g.852G>C and g.709G>A and amino acid changes p.Gln284His and p.Glu237Lys respectively).  Conclusion: We found three novel mutations in Bangladeshi breast cancer patients. This finding indicates the necessity to study the mutation profile of whole BRCA1 gene in our population for cancer risk prediction.

Pathology and Telepathology Methods in the Child Health and Mortality Prevention Surveillance Network.

This manuscript describes the Child Health and Mortality Prevention Surveillance (CHAMPS) network approach to pathologic evaluation of minimally invasive tissue sampling (MITS) specimens, including guidelines for histopathologic examination and further diagnostics with special stains, immunohistochemistry, and molecular testing, as performed at the CHAMPS Central Pathology Laboratory (CPL) at the Centers for Disease Control and Prevention, as well as techniques for virtual discussion of these cases (telepathology) with CHAMPS surveillance locations. Based on review of MITS from the early phase of CHAMPS, the CPL has developed standardized histopathology-based algorithms for achieving diagnoses from MITS and telepathology procedures in conjunction with the CHAMPS sites, with the use of whole slide scanners and digital image archives, for maximizing concurrence and knowledge sharing between site and CPL pathologists. These algorithms and procedures, along with lessons learned from initial implementation of these approaches, guide pathologists at the CPL and CHAMPS sites through standardized diagnostics of MITS cases, and allow for productive, real-time case discussions and consultations.