Preimplantation genetic testing using haplotype-based single nucleotide polymorphisms analysis


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Abstract

Aim. To develop and apply haplotype-based single nucleotide polymorphisms (SNP) analysis for preimplantation genetic testing for monogenic diseases (PGT-M) using chips developed by Affymetrix, Inc., USA. Materials and methods. Twenty-three families with monogenic pathology underwent testing with an integrated approach simultaneously using PGT-M (fragment analysis of STR markers, SNP haplotyping, Sanger sequencing, real-time PCR) and PGTfor aneuploidy (PGT-A) (NGS and aCGH). Results. Out of 93 embryos sent for testing, 55 were euploid. In three families, OGT-M was not performed due to the complete absence of euploid embryos after OGT-A. In the remaining 20 observations, 38 embryos (20 without mutations and 18 with heterozygous carriers) were transferred into the uterine cavity. Interpretation of SNP haplotyping results was more straightforward and reliable than the STR analysis. This technique is universal and does not require individual development for each case. The results of SNP haplotyping are described in detail for two cases, including PGT-M for achondroplasia (autosomal dominant inheritance) and galactosemia (recessive inheritance). Conclusion. The versatility and reliability of the developed approach significantly accelerate obtaining the results, facilitating their interpretation, and reducing the likelihood of possible errors. Also, OGT-M should be preceded by OGT-A for the prevention of chromosomal pathology.

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About the authors

A. N Ekimov

V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: a_ekimov@oparina4.ru
Clinical Geneticist at the Molecular Genetics Laboratory 4, Ac. Oparin str., Moscow, Russian Federation, 117997

N. A Karetnikova

V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: n_karetnikova@oparina4.ru
Clinical Geneticist at the Molecular Genetics Laboratory 4, Ac. Oparin str., Moscow, Russian Federation, 117997

E. S Shubina

V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: e_shubina@oparina4.ru
Head of Genomic Data Analysis Laboratory 4, Ac. Oparin str., Moscow, Russian Federation, 117997

A. Yu Gol'tsov

V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: andrey.goltsov@gmail.com
Researcher at the Molecular Genetics Laboratory 4, Ac. Oparin str., Moscow, Russian Federation, 117997

M. V Kuznetsova

V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: mkarja@mail.ru
Ph.D. (biol.sci.), Senior Researcher at the Molecular Genetics Laboratory 4, Ac. Oparin str., Moscow, Russian Federation, 117997

I. S Mukosei

V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: irina.mukosey@yandex.ru
Researcher at the Molecular Genetics Laboratory 4, Ac. Oparin str., Moscow, Russian Federation, 117997

O. V Ritcher

V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: o_ritcher@oparina4.ru
Clinical Laboratory Pathologist at the Molecular Genetics Laboratory 4, Ac. Oparin str., Moscow, Russian Federation, 117997

D. Yu Trofimov

V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: d_trofimov@oparina4.ru
Professor, Head of the Institute of Reproductive Genetics 4, Ac. Oparin str., Moscow, Russian Federation, 117997

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