Huntington disease (HD) is the most common monogenic neurodegenerative disorder in populations of European ancestry, but occurs at lower prevalence in populations of East Asian or black African descent. New mutations for HD result from CAG repeat expansions of intermediate alleles (IAs), usually of paternal origin. The differing prevalence of HD may be related to the rate of new mutations in a population, but no comparative estimates of IA frequency or the HD new mutation rate are available. In this study, we characterize IA frequency and the CAG repeat distribution in fifteen populations of diverse ethnic origin. We estimate the HD new mutation rate in a series of populations using molecular IA expansion rates. The frequency of IAs was highest in Hispanic Americans and Northern Europeans, and lowest in black Africans and East Asians. The prevalence of HD correlated with the frequency of IAs by population and with the proportion of IAs found on the HD‐associated A1 haplotype. The HD new mutation rate was estimated to be highest in populations with the highest frequency of IAs. In European ancestry populations, one in 5,372 individuals from the general population and 7.1% of individuals with an expanded CAG repeat in the HD range are estimated to have a molecular new mutation. Our data suggest that the new mutation rate for HD varies substantially between populations, and that IA frequency and haplotype are closely linked to observed epidemiological differences in the prevalence of HD across major ancestry groups in different countries.

Background Huntington’s disease (HD) is diagnosed in 1 in 7300 individuals in Western populations but the frequency and penetrance of the causative CAG repeat expansion is unknown. Effects of population ageing, which may increase the rate of late-onset HD, remain unclear. Aims To directly estimate the frequency and penetrance of CAG repeat alleles associated with HD, and model changes in prevalence resulting from increased ascertainment of late-onset cases. Methods CAG repeat length was evaluated in 7315 individuals from three population-based cohorts in British Columbia, the United States, and Scotland. The frequency of CAG 36–38 repeat genotypes was compared to the prevalence of HD patients with genetically confirmed CAG 36–38 in a multisource clinical ascertainment in British Columbia, Canada. Penetrance of 36–38 CAG repeat alleles for HD was directly estimated for individuals ≥65 years of age. Age-specific prevalence rates were used to model change in prevalence as a function of population ageing and increased ascertainment of patients ≥65 years of age. Results 18 of 7315 individuals had ≥36 CAG, revealing that approximately 1 in 400 individuals in the general population have an expanded CAG repeat associated with HD (0.246%). Individuals with CAG 36–37 genotypes are the most common (36, 0.096%; 37, 0.082%; 38, 0.027%; 39, 0.000%; ≥40, 0.041%). The prevalence of HD is expected to increase as a result of both population ageing and increased ascertainment of late-onset cases. Conclusions The relatively infrequent diagnosis of HD at 36–38 CAG repeats suggests low penetrance in this range. Another contributing factor may be reduced ascertainment of HD in those of older age. Our data imply that population ageing will lead to higher prevalence rates of HD. Improved ascertainment of late-onset HD, particularly in the reduced penetrance range, may lead to further increases.

Biorepository processing includes nucleic acid extractions in batch mode from a large number of blood samples from many different donors. Handling such a large number of biospecimens presents the challenge of ensuring that samples are not switched or mislabeled during processing. One approach for confirming donor identity from DNA samples is the use of multiplexed fluorescent PCR for detecting Short Tandem Repeat (STR) allelic-size polymorphisms for a set of common autosomal loci. While donor identity of DNA extracted directly from blood collected in standard tubes containing anticoagulants can be easily verified by generating STR profiles, RNA from blood collected in PAXgene Blood RNA tubes (PAXgene RNA tubes) is depleted of DNA and is not amenable to STR fingerprinting for donor identity verification. We investigated the feasibility of isolating DNA directly from blood collected in PAXgene RNA tubes for use as template for STR DNA fingerprinting for blood donor identity verification. We determined that DNA extraction can be performed manually with the QIAamp DNA Blood Minikit or on the QIAxtractor instrument with minimal pre-processing protocol additions, and that DNA isolated from blood collected in PAXgene RNA tubes is of sufficient quantity and quality for successful STR fingerprint analysis. Adaptation of quality assurance methods such as the PAXgene RNA tube DNA extraction/STR fingerprinting assay described here is a good practice that ensures that biobanking collections provide scientists with high quality, donor-verified biomaterial.

When a biological specimen is donated to a biobank such as the nonprofit Coriell Institute for Medical Research, regardless of whether that submission is sent directly or through a physician, scientist, foundation, or patient-centered advocacy organization, the donor expects their biomaterial to be processed effectively and stored in proper conditions until distribution to researchers answering scientific questions. The donor and scientific researchers rarely, if ever, consider what might happen to those specimens if the biobank experiences an adverse event, such as a disaster that compromises its business operations, including handling of samples. Management of biomaterials is not simply a laboratory process; their long-term survival is dependent on both the laboratory preparation and the infrastructure designed for maintenance, safety, and security. Coriell Institute has documented disaster preparedness plans since its inception in 1953, and currently manages hundreds of thousands of cell lines and DNA samples under ISO 9001 quality management standards, complete with a robust Emergency Operations Plan. The Institute's recent approach to preparing for Hurricane Sandy, a Category 1 hurricane that struck the East Coast of the United States in late October 2012, was two-fold. It included the validation of its long-term strategies focused on emergency back-up systems, communication solutions, and employee training, and implementation of short-term tactics such as confirming on-call emergency response personnel and safe storage options for working biomaterials and reagents. The purpose of this article is to review several best practices in use at Coriell Institute associated with disaster planning and to identify and evaluate the effectiveness of those elements in coping with Hurricane Sandy.

Background Genetic ancestry is known to impact outcomes of genotype-phenotype studies that are designed to identify risk for common diseases in human populations. Failure to control for population stratification due to genetic ancestry can significantly confound results of disease association studies. Moreover, ancestry is a critical factor in assessing lifetime risk of disease, and can play an important role in optimizing treatment. As modern medicine moves towards using personal genetic information for clinical applications, it is important to determine genetic ancestry in an accurate, cost-effective and efficient manner. Self-identified race is a common method used to track and control for population stratification; however, social constructs of race are not necessarily informative for genetic applications. The use of ancestry informative markers (AIMs) is a more accurate method for determining genetic ancestry for the purposes of population stratification. Methodology/Principal Findings Here we introduce a novel panel of 36 microsatellite (MSAT) AIMs that determines continental admixture proportions. This panel, which we have named Continental Ancestry Informative Markers or CoAIMs, consists of MSAT AIMs that were chosen based upon their measure of genetic variance (Fst), allele frequencies and their suitability for efficient genotyping. Genotype analysis using CoAIMs along with a Bayesian clustering method (STRUCTURE) is able to discern continental origins including Europe/Middle East (Caucasians), East Asia, Africa, Native America, and Oceania. In addition to determining continental ancestry for individuals without significant admixture, we applied CoAIMs to ascertain admixture proportions of individuals of self declared race. Conclusion/Significance CoAIMs can be used to efficiently and effectively determine continental admixture proportions in a sample set. The CoAIMs panel is a valuable resource for genetic researchers performing case-control genetic association studies, as it can control for the confounding effects of population stratification. The MSAT-based approach used here has potential for broad applicability as a cost effective tool toward determining admixture proportions.