Runs of homozygosity in spontaneous abortions from families with recurrent pregnancy loss
Recurrent pregnancy loss (RPL) is a severe reproductive pathology with a significant component of unexplained etiology. Extended homozygous regions as a possible etiological factor for RPL were sought in the genomes of embryos. Twenty-two paired first-trimester spontaneously aborted embryos from ele...
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| Format: | Article |
| Language: | English |
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Siberian Branch of the Russian Academy of Sciences, Federal Research Center Institute of Cytology and Genetics, The Vavilov Society of Geneticists and Breeders
2019-03-01
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| Series: | Вавиловский журнал генетики и селекции |
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| Online Access: | https://vavilov.elpub.ru/jour/article/view/1943 |
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| author | N. A. Skryabin S. A. Vasilyev T. V. Nikitina D. I. Zhigalina R. R. Savchenko N. P. Babushkina M. E. Lopatkina A. A. Kashevarova I. N. Lebedev |
| author_facet | N. A. Skryabin S. A. Vasilyev T. V. Nikitina D. I. Zhigalina R. R. Savchenko N. P. Babushkina M. E. Lopatkina A. A. Kashevarova I. N. Lebedev |
| author_sort | N. A. Skryabin |
| collection | DOAJ |
| description | Recurrent pregnancy loss (RPL) is a severe reproductive pathology with a significant component of unexplained etiology. Extended homozygous regions as a possible etiological factor for RPL were sought in the genomes of embryos. Twenty-two paired first-trimester spontaneously aborted embryos from eleven women with recurrent miscarriage were analyzed. All embryos had normal karyotypes according to metaphase karyotyping and conventional comparative genomic hybridization. SurePrint G3 Human CGH + SNP 4 × 180K microarrays (Agilent Technologies) were used to search for homozygous regions. As a result, 39 runs of homozygosity (ROH) were identified in extraembryonic tissues of 15 abortuses. Verification of recurrent homozygous regions was performed by Sanger sequencing. The presence of occasional heterozygous SNPs was shown in 25 extended ROHs, which may indicate that they did not arise de novo but were inherited from parents. In the course of inheritance in a series of generations, they may accumulate mutations, leading to heterozygosity for several sites in the initially homozygous population-specific regions. Homozygotization of recessive mutations is one of the putative mechanisms of the influence of such inherited ROHs on RPL development. The high frequency of extended ROHs detected in the present study may point to a role of inbreeding in RPL etiology. Homozygous regions may also occur due to uniparental disomy, and abnormalities of genomic imprinting may be another mechanism responsible for the pathological manifestation of ROHs in embryogenesis. Indeed, five predicted imprinted genes were identified within ROHs according to the Geneimprint database: OBSCN, HIST3H2BB, LMX1B, CELF4, and FAM59A. This work reports the first finding of a high frequency of extended ROHs in spontaneously aborted embryos with normal karyotypes from families with RPL. |
| format | Article |
| id | doaj-art-baac6f4e959c4f66ba4e0f71b76dcf5c |
| institution | Kabale University |
| issn | 2500-3259 |
| language | English |
| publishDate | 2019-03-01 |
| publisher | Siberian Branch of the Russian Academy of Sciences, Federal Research Center Institute of Cytology and Genetics, The Vavilov Society of Geneticists and Breeders |
| record_format | Article |
| series | Вавиловский журнал генетики и селекции |
| spelling | doaj-art-baac6f4e959c4f66ba4e0f71b76dcf5c2025-02-01T09:58:07ZengSiberian Branch of the Russian Academy of Sciences, Federal Research Center Institute of Cytology and Genetics, The Vavilov Society of Geneticists and BreedersВавиловский журнал генетики и селекции2500-32592019-03-0123224424910.18699/VJ19.489899Runs of homozygosity in spontaneous abortions from families with recurrent pregnancy lossN. A. Skryabin0S. A. Vasilyev1T. V. Nikitina2D. I. Zhigalina3R. R. Savchenko4N. P. Babushkina5M. E. Lopatkina6A. A. Kashevarova7I. N. Lebedev8Research Institute of Medical Genetics, Tomsk National Research Medical Center, RAS.Research Institute of Medical Genetics, Tomsk National Research Medical Center, RAS.Research Institute of Medical Genetics, Tomsk National Research Medical Center, RAS.Research Institute of Medical Genetics, Tomsk National Research Medical Center, RAS.Research Institute of Medical Genetics, Tomsk National Research Medical Center, RAS.Research Institute of Medical Genetics, Tomsk National Research Medical Center, RAS.Research Institute of Medical Genetics, Tomsk National Research Medical Center, RAS.Research Institute of Medical Genetics, Tomsk National Research Medical Center, RAS.Research Institute of Medical Genetics, Tomsk National Research Medical Center, RAS.Recurrent pregnancy loss (RPL) is a severe reproductive pathology with a significant component of unexplained etiology. Extended homozygous regions as a possible etiological factor for RPL were sought in the genomes of embryos. Twenty-two paired first-trimester spontaneously aborted embryos from eleven women with recurrent miscarriage were analyzed. All embryos had normal karyotypes according to metaphase karyotyping and conventional comparative genomic hybridization. SurePrint G3 Human CGH + SNP 4 × 180K microarrays (Agilent Technologies) were used to search for homozygous regions. As a result, 39 runs of homozygosity (ROH) were identified in extraembryonic tissues of 15 abortuses. Verification of recurrent homozygous regions was performed by Sanger sequencing. The presence of occasional heterozygous SNPs was shown in 25 extended ROHs, which may indicate that they did not arise de novo but were inherited from parents. In the course of inheritance in a series of generations, they may accumulate mutations, leading to heterozygosity for several sites in the initially homozygous population-specific regions. Homozygotization of recessive mutations is one of the putative mechanisms of the influence of such inherited ROHs on RPL development. The high frequency of extended ROHs detected in the present study may point to a role of inbreeding in RPL etiology. Homozygous regions may also occur due to uniparental disomy, and abnormalities of genomic imprinting may be another mechanism responsible for the pathological manifestation of ROHs in embryogenesis. Indeed, five predicted imprinted genes were identified within ROHs according to the Geneimprint database: OBSCN, HIST3H2BB, LMX1B, CELF4, and FAM59A. This work reports the first finding of a high frequency of extended ROHs in spontaneously aborted embryos with normal karyotypes from families with RPL.https://vavilov.elpub.ru/jour/article/view/1943recurrent pregnancy lossarray-based comparative genomic hybridizationruns of homozygosityspontaneous abortionsgenomic imprinting |
| spellingShingle | N. A. Skryabin S. A. Vasilyev T. V. Nikitina D. I. Zhigalina R. R. Savchenko N. P. Babushkina M. E. Lopatkina A. A. Kashevarova I. N. Lebedev Runs of homozygosity in spontaneous abortions from families with recurrent pregnancy loss Вавиловский журнал генетики и селекции recurrent pregnancy loss array-based comparative genomic hybridization runs of homozygosity spontaneous abortions genomic imprinting |
| title | Runs of homozygosity in spontaneous abortions from families with recurrent pregnancy loss |
| title_full | Runs of homozygosity in spontaneous abortions from families with recurrent pregnancy loss |
| title_fullStr | Runs of homozygosity in spontaneous abortions from families with recurrent pregnancy loss |
| title_full_unstemmed | Runs of homozygosity in spontaneous abortions from families with recurrent pregnancy loss |
| title_short | Runs of homozygosity in spontaneous abortions from families with recurrent pregnancy loss |
| title_sort | runs of homozygosity in spontaneous abortions from families with recurrent pregnancy loss |
| topic | recurrent pregnancy loss array-based comparative genomic hybridization runs of homozygosity spontaneous abortions genomic imprinting |
| url | https://vavilov.elpub.ru/jour/article/view/1943 |
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