November is the month where we pause to reflect on what we are thankful for. At Golden Helix, we are thankful for the many dedicated scientists and practitioners who are tirelessly working on new discoveries to enhance the lives of humans and preserve our food supply in the face of ever-changing conditions in agriculture. As always, we are proud to support their efforts and wish them continued success!
Diagnostic Pitfalls in Vitamin B6-dependent Epilepsy Caused by Mutations in the PLPBP Gene
Researchers from Denmark and Sweden teamed up to better understand the hidden causes of vitamin B6-dependent epilepsy in neonatal patients. Using VarSeq to perform variant prioritization during their exome sequence testing, the team identified a homozygous splice-site variant in the pyrodoxal phosphate homeostasis protein (PLPBP) gene. Vitamin B6-responsive or Pyridoxin-responsive epilepsies are a group of genetic disorders that manifest as seizures usually shortly after birth. The seizures are nonresponsive to treatment with common antiepileptic drugs. The diagnosis of this condition is sometimes confounded by the lack of metabolic biomarkers that can be used for early detection, which is key for employing effective treatments. The data from this study supports further investigation of PLPHP deficiency to optimize treatment strategies and to identify additional biomarkers to speed diagnosis. The data also supports the administration of a trial with vitamin B6 for patients who present with symptoms where initial common treatments fail.
Mads Bak, Jacob Ek & Colleagues, Copenhagen University Hospital / Published in JIMD Reports
Genetic and Epigenetic Study of an Alzheimer’s Disease Family with Monozygotic Triplets
Monozygotic siblings offer the best opportunity to study risk/protective factors in disease development, so a multinational team of researchers took advantage of a rare opportunity to study a family which included monozygotic triplets, with a family history of Alzheimer’s disease. Their methods included clinical, genetic and epigenetic analyses of the triplets, two of whom were diagnosed with late-onset slow-progressing Alzheimer’s disease, alongside an offspring of one of the triplets that demonstrated early-onset symptoms. With the help of VarSeq’s CNV calling tool in their genetic analyses, the team was able to catalog over 50 possibly damaging variants which warrant further investigation. The data presented in this study will become part of a much larger, ongoing whole-genome sequencing Alzheimer’s disease project and may help to unlock the mystery surrounding factors that are linked to age at onset of this devastating disease.
John Robinson & Colleagues, Robarts Research Institute / Published in BRAIN – A Journal of Neurology
BAP1 Tumor Predisposition Syndrome Case Report: pathological and clinical aspects of BAP1-inactivated melanocytic tumors (BIMTs), including dermoscopy and confocal microscopy
A team of researchers from A. C. Camargo Cancer Center in Brazil was able to identify a novel pathogenic germline variant present in a family with a history of BAP1-inactivated melanocytic tumors (BIMTs), cutaneous melanomas and mesotheliomas. The team employed VarSeq to prioritize the variants when performing the germline genetic analysis of the affected family. Since the presence of BIMTs emerge earlier than BAP1- associated tumors and can also be associated with high frequency with BAP1 tumor predisposition syndrome (BAP1-TPDS), the data suggests that BIMTs may be used as an early biomarker for BAP1 germline mutations. BAP1-TPDS has previously been associated with the onset of melanocytic tumor, malignant mesotheliomas, renal cell carcinoma, and potentially other cutaneous & internal malignancies. The findings of this study may lead to earlier detection of risk factors for potentially aggressive tumors in high-risk patients.
Dirce Carraro & Colleagues, A. C. Camargo Cancer Center / Published in BMC Cancer
Genetic Analysis of Novel Phenotypes for Farm Animal Resilience to Weather Variability
Researchers in Scotland sought to minimize the detrimental effects of climate change on farm animal performance by developing novel animal resilience phenotypes and examining their genetic parameters. Using a closely monitored dairy goat herd, the team measured individual animal responses to changes in atmospheric temperature and the temperature-humidity index, then used a genome-wide association study to examine several candidate genes related to animal resilience to environmental change. With the help of SVS software, the team identified several genomic markers associated with resilience phenotypes. These findings support the significance of selective breeding for enhanced animal resilience to weather changes, thus leading to more stable animal performance which is unaffected by weather variability. The team hopes their findings will offer a complementary strategy to reducing greenhouse gas emissions to help offset the detrimental effects of climate change on livestock production.
Joanne Conington & Sebastian Mucha, Scotland Rural College / Published in BMC Genetics
Identification of New Loci for Salt Tolerance in Soybean by High-Resolution Genome-Wide Association Mapping
Led by plant scientists at the University of Missouri, a US team sought to learn more about salt tolerance in soybeans to improve the quality of soybean cultivars. Salinity is considered a major physical stress in crop agriculture all over the world, and with 1128 million hectares of agricultural land considered salt-affected, exploiting plant salinity tolerance may be one effective strategy which could be used to increase crop productivity in saline regions. Using SVS software to overcome the typical concerns (false positive or Type I error) when using GWAS analysis instead of linkage mapping techniques, the team used efficient mixed-model association expedited (EMMAX) and multi-locus mixed model (MLMM) during their investigation and were able to perform two separate GWAS studies simultaneously. The results of this study will open the door to a deeper understanding of how to limit crop losses from naturally occurring salinity as well as from the threat of human activities coupled with global climate changes.
Tri Vuong & Colleagues, University of Missouri / Published in BMC Genomics
Identification of Loci Associated with Conception Rate in Primiparous Holstein Cows
Dairy farmers in the United States are plagued with the problem of subfertility in their herds, which results in increased veterinary costs, high culling and replacement rates, and requires additional inseminations to achieve pregnancy which are costly. All these things affect the bottom line for hard-working farmers. Animal scientists from Washington, Idaho, and Missouri collaborated to study the genetics underlying the physiological processes of dairy cow conception. Using SVS software, the team performed genome-wide association analysis with the EMMAX algorithm. (You can read more about their other uses of SVS by clicking here.) They were ultimately able to identify candidate genes, providing data which can be used in genomic selection for favorable fertility rates. In addition, their findings suggest that using these genes in breeding programs will not have a negative effect on the genes currently used for selection for milk production, providing dairy farmers with a more comprehensive tool for selecting suitable livestock for their operations.
Jennifer Kiser, Holly Neibergs & Colleagues, Washington State University / Published in BMC Genomics
To access the complete list of publications citing Golden Helix products, please visit our Published Articles page on our website.