మాలిక్యులర్ మరియు జెనెటిక్ మెడిసిన్

The increasing prevalence of type 2 diabetes (T2D) underlines the urgent need for proactive strategies to prevent and control T2D. A fairly large number of studies show that T2D is a complex metabolic disease caused by lifestyle, environment and genetic factors. Thus, the study of a genetic predisposition to diabetes is of great importance. At the same time, one of the most effective methods, besides genome-wide researches, is the use of polymorphic markers of various candidate genes, i.e., those genes, protein products of which (enzymes, regulatory proteins and peptides, structural proteins) can be potentially involved in the development of this disease. The study of genetic markers of type 2 diabetes association is relevant worldwide. The aim of this study was to search for genetic markers associated with the development of T2D in individuals of the Kazakh population.

Introduction: Chromosomal mosaicism is characterized by the presence of more than one chromosomally different cell line in an individual. Preimplantation chromosomal mosaicism is characterized by the presence of a mixture of chromosomally different cell lines in an embryo. Studies show that mosaicism for whole chromosomes (aneuploidies) in one or more cells (blastomeres) occurred in more than 75% of cleavage stage embryos, whilst 3%-24% of blastocyst stage embryos are chromosomally mosaic.

Aim: The purpose of this study was to standardize and validate a Next Generation Sequencing (NGS) method for comprehensive chromosome testing for aneuploidies and to study the level of mosaicism in cleavages stage vs. blastocyst stage embryos.

Methods: The validation involved a retrospective blind assessment of whole genome amplification (WGA) products from 14 cleavages stage embryo biopsies (blastomeres), 6 blastocyst stage embryo biopsies (TE), in addition to their 20 discarded blastocyst stage whole embryos. 42.8% of the cleavages stage embryos showed mosaicism, whilst results between the trophectoderm (TE) biopsies (TEB) and their whole embryos at blastocyst stage showed total concordance as no mosaicism was observed. NGS sensitivity and specificity for calling aneuploidy was found to be 100%.

Conclusion: This is the first study reporting preclinical validation and accuracy assessment of the Ion semiconductor sequencing technology in studying the level of mosaicism in cleavage stage and TE biopsies blastocyst stage embryos vs. their whole embryos.

The high level of mosaicism in cleavages stage embryos compared to blastocyst stage embryos does not recommend the PGT-A to be performed on cleavage stage embryos. The NGS proved to be a robust methodology in clinical application of PGT-A.

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????????? ????? ????????: ???????? ?????????????-???? ???????????????? (LC-MS) ?????? ????‌?????????? ??????????????‌?? ??-???? GC (> 100 mg ?????????????? ???????????)?? ??????? ?????????? ???? ????? ??????? 116 ???? ????? ????? ???? ????????????????. ????????? ???? ????‌????‌?? ????? 3 ????? ????-??? ???????? ?????????????. 52 ???? ?????? GIDM?? ????????? ?????? ????? 64 ???? ??????? (???????? ?????). ?????????? ????????? ????? ????? ???????????? ????? ??????????????? ????? ?????? ??????? ??????? ?????????? ?????? ???? ??????? ???? ?????? (n = 6) ????? ???? ??????? (n = 107) ???? ????? ????? ?????? ????????????????.
??????? ????? ????: ????? ?????????? ???? ?????????? GIDM ??????????? ????????????. ? ?????????? ????????? ??????????? ???????????????. ????-?????????? ?????? GIDM?? ????? ????????????? ????? ??? T2DM?? ??????? ?????? ????? ???????? ???????. ??? T2DM ????? GIDM ????? ???????? ???????? ???????? ?????????? ?????? ????????. ?? ??????? ????? ??????????? ?????????? ???? ???????, ????? ?????????? ????? ????????‌? ?????? ????????? ???????????, ??????????????? ??????????‌? ????? ???????????????, ? ??????????‌??? ?????????????. ???????: T2DM???? ?????? ???????? ???????? GIDM?? ????? ?????? ?? ???? ???????????. GIDM T2DM ????? ???????? ??????????????? ????? ????????? ?????????? ??? ?????? ????????. ????, ????????? ???????????? ????? GIDM ??????? ???? ??????? ????????? ?????? ????? ?? ???? ???????????.

?????????: ????????? ???????? ????? ???????? ??????? ????????? ???????????? ???????? (MMF) ????????????? ???? ???????? ??????????? ? ??????? ????? ???????.

????????: UGT1A8, UGT1A9, UGT2B7, ABCC2, IMPDH1 ????? IMPDH2 ???????? ????? ????????, ????????? ??????? ????????? ????? ?????????????‌?? ????????????????. ?????????? ????????? ????????? ????? ?????????? ???????.

???????: ???? ???? ????????? ???????? ?????? ???????????? ????? 28/83 (33%) ?????? MMF ??????????? ????????? ????????? ???? ????-??? ?????? ?????????-?????? ??????????? EC-MPS?? ??????. ????????????? ??????????, IMPDH2 IVS7 + 10 T>C ????????‌?? ????? ???? ABCC2 -24CC ??????-???? ??????? ??????? ????? ??????? ???????? ???????? ???? .

???????: IMPDH2 (IVS7+10T>C) ????? ABCC2 (c.-24C>T) MMF?? ??????? ?????? ???????? ????????? ?????? ???? ????????????.

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