Genetics of Non-conventional Lipoprotein Fractions
Abstract
Lipoprotein subclass measures associate with cardiometabolic disease risk. Currently, the information that lipoproteins convey on disease risk over that of traditional demographic and lipid measures is minimal, and so their use in clinics is limited. However, lipoprotein subclass perturbations represent some of the earliest manifestations of metabolic dysfunction, and their etiology is partially distinct from lipids, so information on the genetic etiology of lipoproteins offers promise for improved risk prediction, and unique mechanistic insights into IR and atherosclerosis. Here, I review the ge...
Source: Current Genetic Medicine Reports - August 29, 2015 Category: Genetics & Stem Cells Source Type: research
Incidental Findings with Genomic Testing: Implications for Genetic Counseling Practice
Abstract
This paper summarizes the current controversies surrounding the identification and disclosure of “incidental” or “secondary” findings from genomic sequencing and the implications for genetic counseling practice. The rapid expansion of clinical sequencing has influenced the ascertainment and return of incidental findings, while empiric data to inform best practices are still being generated. Using the North Carolina Clinical Genomic Evaluation by Next Generation Exome Sequencing (NCGENES) research project as an example, we discuss the implications of different models of consent and their i...
Source: Current Genetic Medicine Reports - August 24, 2015 Category: Genetics & Stem Cells Source Type: research
Delineation of New Disorders and Phenotypic Expansion of Known Disorders Through Whole Exome Sequencing
Abstract
Whole-exome sequencing (WES) has revolutionized gene discovery in human disease, drastically improving detection of pathogenic variation, expanding the delineation of molecular networks, enriching characterization of genomic architecture and refining the genotype–endophenotype distinctions in heterogeneous phenotypes. WES studies, often aided by collaborative consortia, have proven particularly effective in identifying the genetic etiology of autism, epilepsy, neurodevelopmental disabilities, brain malformations, congenital heart disease, congenital diaphragmatic hernia, multiple congenital ano...
Source: Current Genetic Medicine Reports - August 22, 2015 Category: Genetics & Stem Cells Source Type: research
Current Tools for Interpretation of Genomic Copy Number Variants
Abstract
Genomic microarray analysis has been widely implemented in clinical laboratories for postnatal diagnosis of developmental delay, congenital anomalies and/or autism, and is quickly being adopted in the prenatal setting for fetuses with abnormal ultrasound findings. In comparison to karyotype analysis, the previous gold standard test, there has been a major increase in the amount of data requiring clinical interpretation in clinical laboratories. Although there have been significant improvements in the technologies and algorithms used for detection of copy number variants (CNVs), the assessment of ...
Source: Current Genetic Medicine Reports - August 22, 2015 Category: Genetics & Stem Cells Source Type: research
Expansion and Implications of Newborn Screening
Abstract
Newborn screening (NBS) for phenylketonuria in the early 1960s represented a veritable revolution in public health. It added population screening for prevention of intellectual disability to public health that had been limited to testing and epidemiological follow-up of infectious diseases. Over time, NBS has progressively expanded with additional metabolic and non-metabolic disorders in which early pre-symptomatic detection allows prevention of developmental disability or death. NBS continues to evolve with programs in development to screen for an unprecedented number of conditions. Previ...
Source: Current Genetic Medicine Reports - July 24, 2015 Category: Genetics & Stem Cells Source Type: research
Genetics of Orofacial Cleft Birth Defects
Abstract
Orofacial cleft birth defects (OFCs) are the most common facial birth defects and among the most common of all birth defects. OFCs can occur as isolated, nonsyndromic events or as part of Mendelian syndromes. Notably, many genes that contribute to the etiology of these disorders, both syndromic and nonsyndromic, have now been identified after decades of research using multiple genetic approaches. The pace of gene identification has significantly increased recently due to advances in sequencing and genotyping technologies. Multiple genome-wide association studies of nonsyndromic OFCs have identifi...
Source: Current Genetic Medicine Reports - July 3, 2015 Category: Genetics & Stem Cells Source Type: research
Non-invasive Prenatal Screening for Fetal Aneuploidy: Comparison with Cytogenetic Results
Abstract
Non-invasive prenatal screening (NIPS) for fetal aneuploidy detection using cell-free fetal DNA from maternal circulation has been rapidly adopted for use in high-risk pregnancies since its inception in 2011. While most published NIPS studies are written from the clinical validation, obstetric, or technological viewpoints, in this review we summarize the published cytogenetics laboratory experience with this technology. A total of 528 NIPS positive cases were compared to cytogenetic results and the overall true-positive rate was 77 % (95 % CI 73.3–80.6) for all aneuploidies (407/528). Sixty p...
Source: Current Genetic Medicine Reports - June 30, 2015 Category: Genetics & Stem Cells Source Type: research
Standardizing Variant Interpretation in Genomic Sequencing: Implications for Genetic Counseling Practice
Abstract
The dramatic increase in genetic testing technologies has led to discussion about the roles of genetic counselors and other healthcare providers in variant interpretation. The ability to detect DNA variants greatly surpasses the ability to interpret their clinical impact, limiting the benefit of these technologies. Healthcare providers assisting patients in understanding uncertain genetic test results should be aware of ClinGen and ClinVAR. Challenges include understanding the level of certainty or uncertainty behind the determination of pathogenicity, the variable types of variant assessment per...
Source: Current Genetic Medicine Reports - June 30, 2015 Category: Genetics & Stem Cells Source Type: research
Mosaicism in Traditional Mendelian Diseases
Abstract
Somatic mutations are post-zygotic mutational event that leads to generation of two or more genotypes within an individual. With the recent advances in genomic technologies, there is an increasing recognition of the role of somatic mosaicism in Mendelian disease. Somatic mutation can occur at the chromosomal or the DNA sequence level and the distribution of somatic mosaicism among tissues depends on the timing of the mutation during fetal development. Certain types of somatic mutations are lethal when present in the germline and hence, are only seen in the somatic state, while there are other som...
Source: Current Genetic Medicine Reports - June 20, 2015 Category: Genetics & Stem Cells Source Type: research
Cornelia de Lange Syndrome: A Variable Disorder of Cohesin Pathology
Abstract
Cornelia de Lange syndrome (CdLS) is a rare multiple malformation syndrome including small stature, distinctive craniofacial features, limb anomalies, neurodevelopmental and behavioral abnormalities, and other organ system pathology. Recent literature has demonstrated that typical CdLS and related overlapping disorders display a broad range of severity and pleiotropy, suggesting that considering these diagnoses as a spectrum may be more appropriate. A molecular basis has been identified in many individuals, with mutations in five genes primarily responsible. These genes encode structural or regul...
Source: Current Genetic Medicine Reports - April 24, 2015 Category: Genetics & Stem Cells Source Type: research
Thinking Differently About Genetic Counseling Service Delivery
This article reviews the current status of genetic counseling service delivery including recent innovations. We describe some key factors that affect access and delivery including the time-intensiveness of genetic counseling sessions, the labor intensiveness of case preparation and follow-up services, and geographic barriers. Current remedies for improving access to genetic counseling services and their effectiveness are reviewed. Factors that potentially pose barriers for increasing access, such as reimbursement for services, are discussed. Finally, we propose ways for genetic and non-genetic professionals to work togethe...
Source: Current Genetic Medicine Reports - April 7, 2015 Category: Genetics & Stem Cells Source Type: research
Phenome-Wide Association Studies: Leveraging Comprehensive Phenotypic and Genotypic Data for Discovery
Abstract
With the large volume of clinical and epidemiological data being collected, increasingly linked to extensive genotypic data, coupled with expanding high-performance computational resources, there are considerable opportunities for comprehensively exploring the networks of connections that exist between the phenome and the genome. These networks can be identified through Phenome-Wide Association Studies (PheWAS) where the association between a collection of genetic variants, or in some cases a particular clinical lab variable, and a wide and diverse range of phenotypes, diagnoses, traits, and/or o...
Source: Current Genetic Medicine Reports - April 3, 2015 Category: Genetics & Stem Cells Source Type: research
Is it Time for Genomic Counseling? Retrofitting Genetic Counseling for the Era of Genomic Medicine
Abstract
Over time, there has been a significant increase in clinical genetic testing technologies, including whole exome sequencing and large multi-gene panels, as well as the number of conditions for which testing is available, the settings in which testing is offered, and the utilization of a genotype-first evaluative strategy. Discussing the risks and benefits of each potentially appropriate test, including the possibility for incidental or uncertain findings, has added a level of informational complexity that did not exist when the original models of genetic counseling were developed. We review how g...
Source: Current Genetic Medicine Reports - March 27, 2015 Category: Genetics & Stem Cells Source Type: research
Unique Genetic Counseling Considerations in the Pediatric Oncology Setting
Abstract
Genetic counseling in the pediatric oncology setting involves unique challenges. Various ethical and psychosocial considerations must be taken into account when evaluating minors for hereditary cancer syndromes. Factors that often must be addressed in this setting include issues surrounding if and when to consider genetic testing in affected individuals, limited data and guidelines regarding surveillance or management, predictive testing in at risk minor relatives, access to care, and family dynamics. This paper reviews some of the important considerations for genetic counseling in the pediatric ...
Source: Current Genetic Medicine Reports - March 26, 2015 Category: Genetics & Stem Cells Source Type: research
Breast Cancer Risk Gene Discovery: Opportunities and Challenges
Abstract
DNA-based testing has become routine in modern health care. Today, genetic testing for BRCA1 or BRCA2 germline mutations is routinely offered to women with personal and/or family history of breast cancer (BC) and/or ovarian cancer (OC). The identification of a pathogenic mutation in an index case allows relatives to be offered predictive testing and to provide clinical advice-related risk management to women with a high risk of BC and OC. A pathogenic BRCA1 or BRCA2 mutation is identified in less than 20 % of index cases tested, while variants of unknown biological and clinical significance (VUS...
Source: Current Genetic Medicine Reports - March 24, 2015 Category: Genetics & Stem Cells Source Type: research
