Significance of HLA in the development of Graves’ orbitopathy
January 2023
Authors:
Magdalena Stasiak, Katarzyna Zawadzka-Starczewska, Bogusław Tymoniuk, Bartłomiej Stasiak, Andrzej Lewiński
Abstract:
“Graves’ disease (GD), similarly to most autoimmune disease, is triggered by environmental factors in genetically predisposed individuals. Particular HLA alleles increase or decrease GD risk. No such correlation was demonstrated for Graves’ orbitopathy (GO) in Caucasian population. HLA-A, -B, -C, -DQB1 and -DRB1 genotyping was performed using a high-resolution method in a total number of 2378 persons including 70 patients with GO, 91 patients with non-GO GD and 2217 healthy controls to compare allele frequencies between GO, non-GO and controls. Significant associations between GO and HLA profile were demonstrated, with HLA-A*01:01, -A*32:01, -B*37:01, -B*39:01, -B*42:01, -C*08:02, C*03:02, DRB1*03:01, DRB1*14:01 and DQB1*02:01 being genetic markers of increased risk of GO, and HLA-C*04:01, -C*03:04, -C*07:02 and -DRB1*15:02 being protective alleles. Moreover, correlations between HLA alleles and increased or decreased risk of non-GO GD, but with no impact on risk of GO development, were revealed. Identification of these groups of GO-related and GO-protective alleles, as well as the alleles strongly related to non-GO GD, constitutes an important step in a development of personalized medicine, with individual risk assessment and patient-tailored treatment.”
Sage Science Products:
The Pippin Prep was used in conjunction with the MIA FORA NGS FLEX HT HLA Typing Kit from Immuncor per the manufacturer’s directions.
Author Affiliations:
Polish Mother’s Memorial Hospital – Research Institute, Department of Endocrinology and Metabolic Diseases, Lodz, Poland
Medical University of Lodz, Department of Immunology, Rheumatology and Allergy, Lodz, Poland
Lodz University of Technology, Institute of Information Technology, Lodz, Poland
Medical University of Lodz, Department of Endocrinology and Metabolic Diseases, Lodz, Poland
BMC Research Notes; Genes and Immunity
DOI: 10.1038/s41435-023-00193-z
Proteomic analysis of sialoliths from calcified, lipid and mixed groups as a source of potential biomarkers of deposit formation in the salivary glands
January 2023
Authors:
Natalia Musiał, Aleksandra Bogucka, Dmitry Tretiakow, Andrzej Skorek, Jacek Ryl Gdańsk, Paulina Czaplewska
Abstract:
“Salivary stones, also known as sialoliths, are formed in a pathological situation in the salivary glands. So far, neither the mechanism of their formation nor the factors predisposing to their formation are known despite several hypotheses. While they do not directly threaten human life, they signicantly deteriorate the patient’s quality of life. Although this is not a typical research material, attempts are made to apply various analytical tools to characterise sialoliths and search for the biomarkers in their proteomes. In this work, we used mass spectrometry and SWATH-MS qualitative and quantitative analysis to investigate the composition and select proteins that may contribute to solid deposits in the salivary glands. Twenty sialoliths, previously characterized spectroscopically and divided into the following groups: calcied (CAL), lipid (LIP) and mixed (MIX), were used for the study. Proteins unique for each of the groups were found, including: for the CAL group among them, e.g. proteins from the S100 group (S100 A8/A12 and P), mucin 7 (MUC7), keratins (KRT1/2/4/5/13), elastase (ELANE) or stomatin (STOM); proteins for the LIP group – transthyretin (TTR), lactotransferrin (LTF), matrix Gla protein (MPG), submandibular gland androgen-regulated protein 3 (SMR3A); mixed stones had the fewest unique proteins. Bacterial proteins present in sialoliths have also been identied. The analysis of the results indicates the possible role of bacterial infections, disturbances in calcium metabolism and neutrophil extracellular traps (NETs) in the formation of sialoliths”
Sage Science Products:
The SageELF (3% SDS-Agarase gels) was used for protein separation (10-300 kDa), upstream of Mass Spectrometry.
Author Affiliations:
University of Gdańsk, Poland
Medical University of Gdańsk, Poland
Gdańsk University of Technology, Gdańsk, Poland
Research Square preprint (under review, BMC Clinical Proemics
DOI: 10.21203/rs.3.rs-2471601/v1
Large Cancer Pedigree Involving Multiple Cancer Genes including Likely Digenic MSH2 and MSH6 Lynch Syndrome (LS) and an Instance of Recombinational Rescue from LS
January 2023
Authors:
Ingrid P. Vogelaar, Stephanie Greer, Fan Wang, GiWon Shin, Billy Lau, Yajing H, Sigurdis Haraldsdottir, Rocio Alvarez, Dennis Hazelett, Peter Nguyen, Francesca P. Aguirre, Maha Guindi, Andrew Hendifar, Jessica Balcom, Anna Leininger, Beth Fairbank, Hanlee Ji, Megan P. Hitchins
Abstract:
“Lynch syndrome (LS), caused by heterozygous pathogenic variants affecting one of the mismatch repair (MMR) genes (MSH2, MLH1, MSH6, PMS2), confers moderate to high risks for colorectal, endometrial, and other cancers. We describe a four-generation, 13-branched pedigree in which multiple LS branches carry the MSH2 pathogenic variant c.2006G>T (p.Gly669Val), one branch has this and an additional novel MSH6 variant c.3936_4001+8dup (intronic), and other non-LS branches carry variants within other cancer-relevant genes (NBN, MC1R, PTPRJ). Both MSH2 c.2006G>T and MSH6 c.3936_4001+8dup caused aberrant RNA splicing in carriers, including out-of-frame exon-skipping, providing functional evidence of their pathogenicity. MSH2 and MSH6 are co-located on Chr2p21, but the two variants segregated independently (mapped in trans) within the digenic branch, with carriers of either or both variants. Thus, MSH2 c.2006G>T and MSH6 c.3936_4001+8dup independently confer LS with differing cancer risks among family members in the same branch. Carriers of both variants have near 100% risk of transmitting either one to offspring. Nevertheless, a female carrier of both variants did not transmit either to one son, due to a germline recombination within the intervening region. Genetic diagnosis, risk stratification, and counseling for cancer and inheritance were highly individualized in this family. The finding of multiple cancer-associated variants in this pedigree illustrates a need to consider offering multicancer gene panel testing, as opposed to targeted cascade testing, as additional cancer variants may be uncovered in relatives.”
Sage Science Products:
The HLS-CATCH process (SageHLS system) was used with the 10X Genomics linked read Chromium platform for high resolution haplotype analysis of MSH2 and MSH6 variants (300 kb target, Chr2p21-p16 region).
Author Affiliations:
Department of Medicine (Oncology), Stanford Cancer Institute, Stanford University, Stanford, CA
School of Public Health (Epidemiology), Harbin Medical University, Harbin, China
Bioinformatics and Functional Genomics Center, Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA
Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA
Samuel Oschin Cancer Center, Cedars-Sinai Medical Center, Los Angeles, CA
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN
Minnesota Oncology, Woodbury, MN
Lynch Syndrome Australia, The Summit, QLD, Australia
Stanford Genome Technology Center West, Palo Alto, CA
Lowy Cancer Research Centre, University of New South Wales, Sydney, NSW, Australia
MDPI Cancers
DOI: 10.3390/cancers15010228
Optimising ddRAD sequencing for population genomic studies with ddgRADer
October 2022
Authors:
Aparna Lajmi, Felix Glinka, Eyal Privman
Info:
In this preprint, the authors describe an online webtool that they have developed for designing ddRAD-seq experiments. This webtool assists in the recommendation of restriction enzyme pairs and size-selection criteria. This can assist in make the size selection process more robust, leading to higher sequencing efficiency.
ddgRADer can be accessed here: http://ddgrader.haifa.ac.il/
Author Affiliations:
Department of Evolutionary and Environmental Biology, Institute of Evolution, University of Haifa, Israel
BioRxiv Preprint
DOI: 10.1101/2022.10.08.508655
Heat selection enables highly scalable methylome profiling in cell-free DNA for noninvasive monitoring of cancer patients
September 2022
Authors:
Elsie Cheruba, Ramya Viswanathan, Pui-Mun Wong, Howard John Womersley,
Shuting Han, Brenda Tay, Yiting Lau, Anna Gan, Polly S. Y. Poon, Anders Skanderup,
Sarah B. Ng, Aik Yong Chok, Dawn Qingqing Chong, Iain Beehuat Tan, Lih Feng Cheow
Info:
The authors outline a method (Heatrich-BS) for enriching GC-rich regions (CpG islands) in cell free DNA by heating the sequencing libraries prior to performing bisulfite sequencing. Since methylation profiles are key biomarkers for many cancers, this method provides a low cost and scalable method for clinical assays. The authors also provide an algorithm for monitoring response to colorectal cancer treatment in patients.
BluePippin was used size select the libraries prior to sequencing.
Author Affiliations:
Department of Biomedical Engineering, National University of Singapore
Institute for Health Innovation and Technology, National University of Singapore
Genome Institute of Singapore, Agency for Science, Technology, and Research, Singapore
Division of Medical Oncology, National Cancer Centre Singapore,
Department of Colorectal Surgery, Singapore General Hospital, Singapore
Medical School, National University of Singapore, Singapore
Science Advances
DOI: 10.1126/sciadv.abn4030