About classical molecular genetics, cytogenetic and molecular cytogenetic data not considered by Genome Reference Consortium and thus not included in genome browsers like UCSC, Ensembl or NCBI

Background The Genome Reference Consortium (GRC) has according to its own statement the “mission to improve the human reference genome assembly, correcting errors and adding sequence to ensure it provides the best representation of the human genome to meet basic and clinical research needs”. Data from GRC is included in genome browsers like UCSC (University of California, Santa Cruz), Ensembl or NCBI (National Center for Biotechnology Information) and are thereby bases for scientific and diagnostically working human genetic community. Method Here long standing knowledge deriving from classical molecular genetic, cytogenetic and molecular cytogenetic data, not being considered yet by GRC was revisited. Results There were three major points identified: (1) GRC missed to including three chromosomal subbands, each, for 1q32.1, 2p21, 5q13.2, 6p22.3 and 6q21, which were defined by International System for Human Cytogenetic Nomenclature (ISCN) already back in 1980s; instead GRC included additional 6 subbands not ever recognized by ISCN. (2) GRC defined 34 chromosomal subbands of 0.1 to 0.9 Mb in size, while it is general agreement of cytogeneticists that it unlikely to detect chromosomal aberrations below 1–2 Mb in size by GTG-banding. And (3): still all sequences used in molecular cytogenetic routine diagnostics to detect heterochromatic and/ or pericentromeric satellite DNA sequences within the human genome are not included yet into human reference genome. For those sequences, localization and approximate sizes have been determined in the 1970s to 1990, and if included at least ~ 100 Mb of the human genome sequence could be added to the genome browsers. Conclusion Overall, taking into account the here mentioned points and correcting and including the data will definitely provide to the still not being completely finished mapping of the human genome.

Additional cytogenetic abnormalities in chronic myeloid leukemia; an experience from Pakistan

Objectives: To evaluate the presence and characteristics of additional karyotype abnormalities in chronic myeloid leukaemia cases. Method: The cross-sectional study was conducted at the Department of Cytogenetics and Molecular Pathology, National Institute of Blood Diseases and Bone Marrow Transplant, Karachi, from May 2010 to September 2016 and comprised diagnosed chronic myeloid leukaemiapatients regardless of age and gender.Baseline cytogenetic evaluation was done on overnight, 24-hrs un-stimulated and 72-hrs stimulated bone marrow cultures, and karyotypes were defined according to the International System for Human Cytogenetic Nomenclature2013. Data was analysed using SPSS 23. Results: There were 222 cases with a median age of 38 years (range: 12-84 years). The male-to-female ratio was 1.8:1. Chronic myeloid leukaemiawas detected in 18(8.1%) patients havingadditional cytogenetic abnormalities. Among the patients found positive, cytogenetic type was minor in 10(55.55%), major 3(16.66%), complex 3(16.66%), and variant 2(11.11%). . Conclusion: Additional cytogenetic abnormalitieswere found in 8% of the sample. Key Words: Additional cytogenetic abnormalities, Chronic myelogenous leukaemia, Bone marrow, Cytogenetics.

Aneuploidy Analysis of 5740 Referral Cases: A Triennial Report

Background and Objectives: Aneuploidy is one of the major concerns to cause genetic anomalies. This condition is mostly related to addition and/or deletion with respect to set(s) of chromosomes. Here, we report an analysis of 5740 referral cases during three consecutive years (2015 – 2018) from our Diagnostic Research Center, Ahmedabad for aneuploidy pattern. Methodologies: The patients were asked to fill the necessary forms and their blood (5ml) was drawn for chromosomal studies using the Karyotyping following International System for Human Cytogenetic Nomenclature (ISCN) manual. Results: The data revealed the numerical aberrations for only aneuploidy detected was (3.7%; 211/5740). In this report, constitutional (c) autosomal aneuploidy was 75% (158/211). The total mosaic cases were nine (9/211) comprising constitutive (2) and acquired (7) aneuploidy cases. In autosomal aneuploidy, cT21 was higher (96%; 152/158) than others (4%; 6/158) comparatively. Among cT21 (152), males (76%; 115/152) were more affected than females (24%; 37/152). These statistical data also revealed that acquired chromosomal aneuploidy (leukemia) possessed (25%; 53/211); with more mosaic cases (7/211). Conclusion: Couples with such conditions are eligible for genetic tests and counseling as well as new strategies are urgently to be undertaken by governmental organizations (GOs) and non-governmental organizations (NGOs) for affected families with better personalized and informed decision making. The significance of these data is thus discussed in relation to genetic disorders caused by constitutional and acquired aneuploidy of leukemic blood in this report.

CytoGPS: a web-enabled karyotype analysis tool for cytogenetics

Summary Karyotype data are the most common form of genetic data that is regularly used clinically. They are collected as part of the standard of care in many diseases, particularly in pediatric and cancer medicine contexts. Karyotypes are represented in a unique text-based format, with a syntax defined by the International System for human Cytogenetic Nomenclature (ISCN). While human-readable, ISCN is not intrinsically machine-readable. This limitation has prevented the full use of complex karyotype data in discovery science use cases. To enhance the utility and value of karyotype data, we developed a tool named CytoGPS. CytoGPS first parses ISCN karyotypes into a machine-readable format. It then converts the ISCN karyotype into a binary Loss-Gain-Fusion (LGF) model, which represents all cytogenetic abnormalities as combinations of loss, gain, or fusion events, in a format that is analyzable using modern computational methods. Such data is then made available for comprehensive ‘downstream’ analyses that previously were not feasible. Availability and implementation Freely available at http://cytogps.org.

CytoGPS: A Web-Enabled Karyotype Analysis Tool for Cytogenetics

Karyotype data are the most common form of genetic data that is regularly used clinically. They are collected as part of the standard of care in many diseases, particularly in pediatric and cancer medicine contexts. Karyotypes are represented in a unique text-based format, with a syntax defined by the International System for human Cytogenetic Nomenclature (ISCN). While human-readable, ISCN is not intrinsically machine-readable. This limitation has prevented the full use of complex karyotype data in discovery science use cases. To enhance the utility and value of karyotype data, we developed a tool named CytoGPS. CytoGPS first parses ISCN karyotypes into a machine-readable format. It then converts the ISCN karyotype into a binary Loss-Gain-Fusion (LGF) model, which represents all cytogenetic abnormalities as combinations of loss, gain, or fusion events, in a format that is analyzable using modern computational methods. Such data is then made available for comprehensive “downstream” analyses that previously were not feasible.Availability and ImplementationFreely available at https://[email protected] informationNot applicable

Cytogenetic Technologies and Test Issues

Cytogenetic testing is ordered in a wide range of clinical settings. The primary purpose is to evaluate for constitutional abnormalities. This chapter describes cytogenetic testing methodologies, such as microarray analysis, chromosome analysis, prenatal genetic testing, and fluorescence in situ hybridization, identifying their strengths and limitations, and details specimen processing. It summarizes commonly used nomenclature according to the International System for Human Cytogenetic Nomenclature. The chapter also discusses the criteria that laboratory genetic counselors use for reporting uncertain, novel, or ambiguous results.