TY - JOUR

T1 - The Precise Breakpoint Mapping in Paracentric Inversion 10q22.2q23.3 by Comprehensive Cytogenomic Analysis, Multicolor Banding, and Single-Copy Chromosome Sequencing

AU - Карамышева, Татьяна Витальевна

AU - Татьяна, Гайнер

AU - Елисафенко, Евгений Анатольевич

AU - Трифонов, Владимир Александрович

AU - Закирова, Эльвира Гамиловна

AU - Орищенко, Константин Евгеньевич

AU - Мария, Прохорович А.

AU - Лопаткина, Мария Е.

AU - Скрябин, Николай А.

AU - Лебедев, Игорь Н.

AU - Рубцов, Николай Борисович

N1 - This research was funded by the Ministry of Science and Higher Education of the Russian Federation via the Institute of Cytology and Genetics SB RAS (No. FWNR-2022-0015) for the microdissection and FISH analysis and by the Russian Science Foundation, project No. 21-65-00017 (https://rscf.ru/en/project/21-65-00017/ accessed on 5 November 2022), for the aCGH part of the study. The sequence analysis, bioinformatic analysis, and open access are supported by the Ministry of Science and Higher Education of the Russian Federation, grant No. 2019-0546 (FSUS-2020-0040).

PY - 2022/12/14

Y1 - 2022/12/14

N2 - Detection and precise genomic mapping of balanced chromosomal abnormalities in patients with impaired fertility or a clinical phenotype represent a challenge for current cytogenomics owing to difficulties with precise breakpoint localization in the regions enriched for DNA repeats and high genomic variation in such regions. Here, we present a comprehensive cytogenomic approach to breakpoint mapping in a rare paracentric inversion on 10q (in a patient with oligoasthenoteratozoospermia and necrozoospermia) that does not affect other phenotype traits. Multicolor banding, chromosomal microarray analysis, chromosome microdissection with reverse painting, and single-copy sequencing of the rearranged chromosome were performed to determine the length and position of the inverted region as well as to rule out a genetic imbalance at the breakpoints. As a result, a paracentric 19.251 Mbp inversion at 10q22.2q23.3 was described. The most probable location of the breakpoints was predicted using the hg38 assembly. The problems of genetic counseling associated with enrichment for repeats and high DNA variability of usual breakpoint regions were discussed. Possible approaches for cytogenomic assessment of couples with balanced chromosome rearrangements and problems like reproductive failures were considered and suggested as useful part of effective genetic counseling.

AB - Detection and precise genomic mapping of balanced chromosomal abnormalities in patients with impaired fertility or a clinical phenotype represent a challenge for current cytogenomics owing to difficulties with precise breakpoint localization in the regions enriched for DNA repeats and high genomic variation in such regions. Here, we present a comprehensive cytogenomic approach to breakpoint mapping in a rare paracentric inversion on 10q (in a patient with oligoasthenoteratozoospermia and necrozoospermia) that does not affect other phenotype traits. Multicolor banding, chromosomal microarray analysis, chromosome microdissection with reverse painting, and single-copy sequencing of the rearranged chromosome were performed to determine the length and position of the inverted region as well as to rule out a genetic imbalance at the breakpoints. As a result, a paracentric 19.251 Mbp inversion at 10q22.2q23.3 was described. The most probable location of the breakpoints was predicted using the hg38 assembly. The problems of genetic counseling associated with enrichment for repeats and high DNA variability of usual breakpoint regions were discussed. Possible approaches for cytogenomic assessment of couples with balanced chromosome rearrangements and problems like reproductive failures were considered and suggested as useful part of effective genetic counseling.

KW - array-based comparative genomic hybridization

KW - breakpoint mapping

KW - chromosomal microdissection

KW - inv(10)

KW - multicolor banding

KW - oligoasthenoteratozoospermia

KW - paracentric inversion

KW - reproductive failure

KW - single-copy chromosome sequencing

UR - https://www.scopus.com/record/display.uri?eid=2-s2.0-85144652559&origin=inward&txGid=0889f32fc75d0762d69edf5aef2c2331

UR - https://www.mendeley.com/catalogue/96305e42-d100-37fd-a4f1-b4bd75fb56c6/

U2 - 10.3390/biomedicines10123255

DO - 10.3390/biomedicines10123255

M3 - Article

C2 - 36552011

VL - 10

JO - Biomedicines

JF - Biomedicines

SN - 2227-9059

IS - 12

M1 - 3255

ER -