Detecting Copy Number Variation via Next Generation Technology
Abstract
Purpose of Review
Copy number variants (CNVs), gains and losses of segments of genomic DNA associated with normal phenotypic variation and disease states, are traditionally detected using chromosomal microarrays. Recent bioinformatic advances now allow for the detection of CNVs using next generation sequencing (NGS) data, greatly increasing the clinical utility of NGS tests.
Recent Findings
Though not widespread, clinical diagnostic laboratories have started to implement CNV dete...
Source: Current Genetic Medicine Reports - June 7, 2016 Category: Genetics & Stem Cells Source Type: research
Genetics of Lipid and Lipoprotein Disorders and Traits
Abstract
Purpose of Review
Plasma lipids, namely cholesterol and triglyceride, and lipoproteins, such as low-density lipoprotein (LDL) and high-density lipoprotein, serve numerous physiological roles. Perturbed levels of these traits underlie monogenic dyslipidemias, a diverse group of multisystem disorders. We are on the verge of having a relatively complete picture of the human dyslipidemias and their components.
Recent Findings
Recent advances in genetics of plasma lipids and lipoprote...
Source: Current Genetic Medicine Reports - June 6, 2016 Category: Genetics & Stem Cells Source Type: research
Current Cardiovascular Genetic Counseling
Abstract
Purpose of Review
Genetic counseling is an increasingly important component of cardiovascular care in the era of precision medicine.
Recent Findings
Over the last 15 years, genetic testing for inherited cardiovascular diseases has exponentially increased and as such increased the need for complex genetic discussions with patients and their family members. Inherited cardiovascular conditions have an inherent risk for sudden cardiac death, and explaining the risks to at-risk famil...
Source: Current Genetic Medicine Reports - June 3, 2016 Category: Genetics & Stem Cells Source Type: research
Genetic Testing for Deaf and Hard of Hearing Individuals: Genetic Counseling
Abstract
More than half of human deafness or hard of hearing is attributable to genetic causes. There are over one hundred genes that individually contribute to cochlear function and the absence or alteration of a single gene can result in deafness, making deaf/hard of hearing genetically heterogeneous. This review will cover the genetic heterogeneity of human deafness, the clinical utility of currently available diagnostic testing for deafness, targeted parallel sequencing modalities, as well as challenges to interpretation of testing. As clinical genetics providers, our counseling approach should be fut...
Source: Current Genetic Medicine Reports - March 31, 2016 Category: Genetics & Stem Cells Source Type: research
Family Communication of Genetic Risk: A Personalized Approach
Abstract
Genetic information is changing the practice of medicine by personalizing prevention and treatment decisions based on the genetic profile of the individual. The impact of personalized genetic-based medicine extends beyond the individual to include the family, where knowledge of a genetic predisposition to a disease condition has implications for individuals, their siblings and offspring, and for the identity of the family itself. The quality of the family communication process is important in assuring accuracy of risk information and in maintaining the cohesion of the family unit. However, there ...
Source: Current Genetic Medicine Reports - March 25, 2016 Category: Genetics & Stem Cells Source Type: research
Genetic Testing for Eye Diseases: A Comprehensive Guide and Review of Ocular Genetic Manifestations from Anterior Segment Malformation to Retinal Dystrophy
Abstract
Genetic eye diseases are a heterogeneous group that collectively involve every facet of the eye, ocular adnexa and visual system. An individual condition within this group may be rare or common, have an isolated finding or be part of a syndrome, may severely threaten survivability, significantly affect vision or may have no bearing on visual morbidity. There have been treatment successes and safety reports in clinical trials involving vector-based ocular gene therapies, and there are currently a significant number of loci and genes known to contribute to human ocular disease, many of which have b...
Source: Current Genetic Medicine Reports - March 18, 2016 Category: Genetics & Stem Cells Source Type: research
Genetic and Epigenetic Architecture of Alzheimer ’s Dementia
< h3 class= " a-plus-plus " > Abstract < /h3 > < p class= " a-plus-plus " > Alzheimer ’s disease (AD) is the most common neurodegenerative disease, affecting up to 5 % of the population over 65 years old. It is characterized by the accumulation of amyloid-β peptide and aggregation of hyperphosphorylated tau protein. Mutations in pivotal genes ( < em class= " a-plus-plus " > APP < /em > , < em class= " a-plus-plus " > PSEN1, < /em > and < em class= " a-plus-plus " > PSEN2 < /em > ) result in the autosomal dominant form of the disease; however, the genetic cause of the majority of cases remains unexplained. Advances in...
Source: Current Genetic Medicine Reports - February 29, 2016 Category: Genetics & Stem Cells Source Type: research
Genetic and Epigenetic Architecture of Alzheimer’s Dementia
Abstract
Alzheimer’s disease (AD) is the most common neurodegenerative disease, affecting up to 5 % of the population over 65 years old. It is characterized by the accumulation of amyloid-β peptide and aggregation of hyperphosphorylated tau protein. Mutations in pivotal genes (APP, PSEN1, and PSEN2) result in the autosomal dominant form of the disease; however, the genetic cause of the majority of cases remains unexplained. Advances in genomic techniques have allowed the discovery of common variants that influence susceptibility to AD. In addition, low-frequency and rare variants in a small number of...
Source: Current Genetic Medicine Reports - February 11, 2016 Category: Genetics & Stem Cells Source Type: research
Regulation of Neuronal Gene Expression by Local Axonal Translation
Abstract
RNA localization is a key mechanism in the regulation of protein expression. In neurons, this includes the axonal transport of select mRNAs based on the recognition of axonal localization motifs in these RNAs by RNA-binding proteins. Bioinformatic analyses of axonal RNAs suggest that selective inclusion of such localization motifs in mature mRNAs is one mechanism controlling the composition of the axonal transcriptome. The subsequent translation of axonal transcripts in response to specific stimuli provides precise spatiotemporal control of the axonal proteome. This axonal translation supports lo...
Source: Current Genetic Medicine Reports - February 6, 2016 Category: Genetics & Stem Cells Source Type: research
Whole Genome Sequencing and Newborn Screening
Abstract
Clinical applications of next-generation sequencing are growing at a tremendous pace. Currently, the largest application of genetic testing in medicine occurs with newborn screening through state-mandated public health programs, and there are suggestions that sequencing could become a standard component of newborn care within the next decade. As such, newborn screening may appear to be a logical starting point to explore whole genome and whole exome sequencing on a population level. Yet, there are a number of ethical, social, and legal implications about the use of a mandatory public health scree...
Source: Current Genetic Medicine Reports - February 1, 2016 Category: Genetics & Stem Cells Source Type: research
Ethical Considerations When Including Lysosomal Storage Disorders in Newborn Screening Programs
Abstract
There is essentially unanimous agreement that newborn screening saves lives. Nevertheless, newborn screening—rated as one of the top 10 successes in public health in the first decade of the twenty-first century by the Centers for Disease Control and Prevention (Koppaka in JAMA 306(5):484–487, 2003)—faces multiple challenges, including questions about how conditions are added to the list of disorders for which screening is done in each state, about the need for parental consent for use of dried blood spots after screening, and the roles of parents in expansion of newborn screening. Such ques...
Source: Current Genetic Medicine Reports - October 16, 2015 Category: Genetics & Stem Cells Source Type: research
Genetic Architecture of Complex Human Traits: What Have We Learned from Genome-Wide Association Studies?
Abstract
Genome-wide association studies have identified thousands of genetic variants associated with various complex human traits and diseases. These results opened a window to the genetic architecture of complex human traits. The fact that the identified variants usually confer small effects and explain only a small fraction of heritability has led the discussion of where to find the ‘missing heritability.’ Two competitive models have been proposed: the ‘infinitesimal model’ suggests large number of variants of small effects and the ‘rare variant model’ suggests multiple large-effect rare v...
Source: Current Genetic Medicine Reports - October 14, 2015 Category: Genetics & Stem Cells Source Type: research
Genetics and Pathology of Chronic Traumatic Encephalopathy
(Source: Current Genetic Medicine Reports)
Source: Current Genetic Medicine Reports - September 23, 2015 Category: Genetics & Stem Cells Source Type: research
Mixed Ancestry and Disease Risk Transferability
Abstract
Ancestry is the series of ancestors who form a line of descent or lineage back to an arbitrary founder or founding population. In recent years, integration of genome-wide genotype and sequence data from multiple populations worldwide has provided much insight into the identities and distributions of ancestral populations or clusters, thereby improving our understanding of historical migrations and current population structure at a sub-continental or regional level. Genetic ancestry, distinct from self-reported ancestry or ethnicity, serves both as a confounder in genetic association studies of ge...
Source: Current Genetic Medicine Reports - September 11, 2015 Category: Genetics & Stem Cells Source Type: research
Understanding the Basics of NGS: From Mechanism to Variant Calling
Abstract
Identifying disease-causing mutations in DNA has long been the goal of genetic medicine. In the last decade, the toolkit for discovering DNA variants has undergone rapid evolution: mutations that were historically discovered by analog approaches like Sanger sequencing and multiplex ligation-dependent probe amplification (“MLPA”) can now be decoded from a digital signal with next-generation sequencing (“NGS”). Given the explosive growth of NGS-based tests in the clinic, it is of the utmost importance that medical practitioners have a fundamental understanding of the newest NGS methodologie...
Source: Current Genetic Medicine Reports - September 4, 2015 Category: Genetics & Stem Cells Source Type: research
