7 research outputs found
Molecular Cytogenetics and Cytogenomics of Brain Diseases
Molecular cytogenetics is a promising field of biomedical research that has recently revolutionized our thinking on genome structure and behavior. This is in part due to discoveries of human genomic variations and their contribution to biodiversity and disease. Since these studies were primarily targeted at variation of the genome structure, it appears apposite to cover them by molecular cytogenomics. Human brain diseases, which encompass pathogenic conditions from severe neurodegenerative diseases and major psychiatric disorders to brain tumors, are a heavy burden for the patients and their relatives. It has been suggested that most of them, if not all, are of genetic nature and several recent studies have supported the hypothesis assuming them to be associated with genomic instabilities (i.e. single-gene mutations, gross and subtle chromosome imbalances, aneuploidy). The present review is focused on the intriguing relationship between genomic instability and human brain diseases. Looking through the data, we were able to conclude that both interindividual and intercellular genomic variations could be pathogenic representing, therefore, a possible mechanism for human brain malfunctioning. Nevertheless, there are still numerous gaps in our knowledge concerning the link between genomic variations and brain diseases, which, hopefully, will be filled by forthcoming studies. In this light, the present review considers perspectives of this dynamically developing field of neurogenetics and genomics
Fluorescence intensity profiles of in situ hybridization signals depict genome architecture within human interphase nuclei
An approach towards construction of two-dimensional (2D) and three-dimensional (3D) profiles of interphase chromatin architecture by quantification of fluorescence in situ hybridization (FISH) signal intensity is proposed. The technique was applied for analysis of signal intensity and distribution within interphase nuclei of somatic cells in different human tissues. Whole genomic DNA, fraction of repeated DNA sequences (Cot1) and cloned satellite DNA were used as probes for FISH. The 2D and 3D fluorescence intensity profiles were able to depict FISH signal associations and somatic chromosome pairing. Furthermore, it allowed the detection of replicating signal patterns, the assessment of hybridization efficiency, and comparative analysis of DNA content variation of specific heterochromatic chromosomal regions. The 3D fluorescence intensity profiles allowed the analysis of intensity gradient within the signal volume. An approach was found applicable for determination of assembly of different types of DNA sequences, including classical satellite and alphoid DNA, gene-rich (G-negative bands) and gene-poor (G-positive bands) chromosomal regions as well as for assessment of chromatin architecture and targeted DNA sequence distribution within interphase nuclei. We conclude the approach to be a powerful additional tool for analysis of interphase genome architecture and chromosome behavior in the nucleus of human somatic cells.ΠΡΠ΅Π΄ΡΡΠ°Π²Π»Π΅Π½ΠΎ ΠΌΠ΅ΡΠΎΠ΄ ΠΏΠΎΠ±ΡΠ΄ΠΎΠ²ΠΈ Π΄Π²ΠΎΠΌΡΡΠ½ΠΈΡ
(2D) ΡΠ° ΡΡΠΈΠΌΡΡΠ½ΠΈΡ
(3D) ΠΏΡΠΎΡΡΠ»ΡΠ² ΡΠ½ΡΠ΅Π½ΡΠΈΠ²Π½ΠΎΡΡΡ ΡΠΈΠ³Π½Π°Π»ΡΠ² ΡΠ»ΡΠΎΡΠ΅ΡΡΠ΅Π½ΡΠ½ΠΎΡ Π³ΡΠ±ΡΠΈΠ΄ΠΈΠ·Π°ΡΡΡ in situ (FISH), ΡΠΎ Π·Π°ΡΠ½ΠΎΠ²Π°Π½ΠΈΠΉ Π½Π° ΠΊΡΠ»ΡΠΊΡΡΠ½ΡΠΉ FISH. ΠΠ°Π²Π΅Π΄Π΅Π½Π° ΠΌΠ΅ΡΠΎΠ΄ΠΈΠΊΠ° Π±ΡΠ»Π° Π²ΠΈΠΊΠΎΡΠΈΡΡΠ°Π½Π° Π΄Π»Ρ Π°Π½Π°Π»ΡΠ·Ρ ΡΠΎΠ·ΡΠ°ΡΡΠ²Π°Π½Π½Ρ ΡΠ° ΡΠΎΠ·ΠΏΠΎΠ΄ΡΠ»Ρ ΡΠΈΠ³Π½Π°Π»ΡΠ² Π² ΡΠ½ΡΠ΅ΡΡΠ°Π·Π½ΠΈΡ
ΡΠ΄ΡΠ°Ρ
ΠΊΠ»ΡΡΠΈΠ½ ΡΡΠ·Π½ΠΈΡ
ΡΠΎΠΌΠ°ΡΠΈΡΠ½ΠΈΡ
ΡΠΊΠ°Π½ΠΈΠ½ Π»ΡΠ΄ΠΈΠ½ΠΈ. ΠΠΈΠΊΠΎΡΠΈΡΡΠ°Π½Π½Ρ 2D ΠΏΡΠΎΡΡΠ»ΡΠ² ΡΠ½ΡΠ΅Π½ΡΠΈΠ²Π½ΠΎΡΡΡ ΠΏΡΠΎΠ΄Π΅ΠΌΠΎΠ½ΡΡΡΡΠ²Π°Π»ΠΎ ΠΌΠΎΠΆΠ»ΠΈΠ²ΡΡΡΡ Π²ΠΈΠ·Π½Π°ΡΠ΅Π½Π½Ρ Π»ΠΎΠΊΠ°Π»ΡΠ·Π°ΡΡΡ FISH-ΡΠΈΠ³Π½Π°Π»ΡΠ². ΠΡΠ»ΡΡ ΡΠΎΠ³ΠΎ, Π΄Π°Π½ΠΈΠΉ ΠΏΡΠ΄Ρ
ΡΠ΄ Π΄ΠΎΠ·Π²ΠΎΠ»ΠΈΠ² ΡΠ΄Π΅Π½ΡΠΈΡΡΠΊΡΠ²Π°ΡΠΈ ΡΠ΅ΠΏΠ»ΡΠΊΠΎΠ²Π°Π½Ρ ΡΠΈΠ³Π½Π°Π»ΠΈ, Π΄Π°ΡΠΈ ΠΎΡΡΠ½ΠΊΡ Π΅ΡΠ΅ΠΊΡΠΈΠ²Π½ΠΎΡΡΡ Π³ΡΠ±ΡΠΈΠ΄ΠΈΠ·Π°ΡΡΡ ΡΠ° ΠΏΡΠΎΠ²Π΅ΡΡΠΈ ΠΏΠΎΡΡΠ²Π½ΡΠ»ΡΠ½ΠΈΠΉ Π°Π½Π°Π»ΡΠ· Π²Π°ΡΡΠ°ΡΡΡ Π²ΠΌΡΡΡΡ ΠΠΠ ΡΠΏΠ΅ΡΠΈΡΡΡΠ½ΠΈΡ
Π΄ΡΠ»ΡΠ½ΠΎΠΊ Ρ
ΡΠΎΠΌΠΎΡΠΎΠΌ. ΠΠΎΠ±ΡΠ΄ΠΎΠ²Π° 3D ΠΏΡΠΎΡΡΠ»ΡΠ² ΠΏΠΎΠΊΠ°Π·Π°Π»Π° ΡΠΎΠ·ΠΏΠΎΠ΄ΡΠ» ΡΠ½ΡΠ΅Π½ΡΠΈΠ²Π½ΠΎΡΡΡ Ρ ΠΌΠ΅ΠΆΠ°Ρ
ΠΏΠ»ΠΎΡΡ ΡΠΈΠ³Π½Π°Π»Ρ. ΠΠΈΠΊΠΎΡΠΈΡΡΠ°Π½Π½Ρ ΡΡΡΡ ΠΌΠ΅ΡΠΎΠ΄ΠΈΠΊΠΈ Π΄ΠΎΠ·Π²ΠΎΠ»ΠΈΠ»ΠΎ Π²ΠΈΠ·Π½Π°ΡΠΈΡΠΈ Π·ΠΎΡΠ΅ΡΠ΅Π΄ΠΆΠ΅Π½Π½Ρ ΡΡΠ·Π½ΠΈΡ
ΡΠΈΠΏΡΠ² ΠΏΠΎΡΠ»ΡΠ΄ΠΎΠ²Π½ΠΎΡΡΠ΅ΠΉ ΠΠΠ: ΠΊΠ»Π°ΡΠΈΡΠ½Π° ΡΠ°ΡΠ΅Π»ΡΡΠ½Π° ΡΠ° Π°Π»ΡΡΠΎΡΠ΄Π½Π° ΠΠΠ; Π³Π΅Π½ΠΎΠ½Π°ΡΠΈΡΠ΅Π½Ρ (G-ΠΏΠΎΠ·ΠΈΡΠΈΠ²Π½Ρ ΠΏΠΎΠ»ΠΎΡΠΈ) Ρ Π³Π΅Π½ΠΎΠ½Π΅Π½Π°ΡΠΈΡΠ΅Π½Ρ (G-Π½Π΅Π³Π°ΡΠΈΠ²Π½Ρ ΠΏΠΎΠ»ΠΎΡΠΈ) Π΄ΡΠ»ΡΠ½ΠΊΠΈ Ρ
ΡΠΎΠΌΠΎΡΠΎΠΌ. ΠΡΡΠΌ ΡΡΠΎΠ³ΠΎ, ΠΌΠ΅ΡΠΎΠ΄ΠΈΠΊΠ° Π½Π°Π΄Π°Π»Π° ΠΌΠΎΠΆΠ»ΠΈΠ²ΡΡΡΡ ΠΎΡΡΠ½ΠΈΡΠΈ ΡΠΎΠ·ΡΠ°ΡΡΠ²Π°Π½Π½Ρ Ρ
ΡΠΎΠΌΠ°ΡΠΈΠ½Π° Π² ΡΠ½ΡΠ΅ΡΡΠ°Π·Π½ΠΈΡ
ΡΠ΄ΡΠ°Ρ
ΡΠΊ ΠΊΡΠ»ΡΡΠΈΠ²ΠΎΠ²Π°Π½ΠΈΡ
, ΡΠ°ΠΊ Ρ Π½Π΅ΠΊΡΠ»ΡΡΠΈΠ²ΠΎΠ²Π°Π½ΠΈΡ
ΠΊΠ»ΡΡΠΈΠ½. ΠΡΠΎΠ±Π»Π΅Π½ΠΎ Π²ΠΈΡΠ½ΠΎΠ²ΠΎΠΊ, ΡΠΎ Π½Π°Π²Π΅Π΄Π΅Π½ΠΈΠΉ ΠΏΡΠ΄Ρ
ΡΠ΄ Ρ Π΅ΡΠ΅ΠΊΡΠΈΠ²Π½ΠΎΡ Π΄ΠΎΠ΄Π°ΡΠΊΠΎΠ²ΠΎΡ ΠΌΠ΅ΡΠΎΠ΄ΠΈΠΊΠΎΡ Π΄Π»Ρ Π²ΠΈΠ²ΡΠ΅Π½Π½Ρ ΡΠ΄Π΅ΡΠ½ΠΎΡ ΠΎΡΠ³Π°Π½ΡΠ·Π°ΡΡΡ, ΡΠΏΠ΅ΡΠΈΡΡΠΊΠΈ Π²Π°ΡΡΠ°ΡΡΡ ΡΠ° ΡΠΎΠ·ΡΠ°ΡΡΠ²Π°Π½Π½Ρ ΠΏΠΎΡΠ»ΡΠ΄ΠΎΠ²Π½ΠΎΡΡΠ΅ΠΉ ΠΠΠ Π² ΡΠ½ΡΠ΅ΡΡΠ°Π·Π½ΠΈΡ
ΡΠ΄ΡΠ°Ρ
, Π° ΡΠ°ΠΊΠΎΠΆ ΠΏΠΎΠ²Π΅Π΄ΡΠ½ΠΊΠΈ ΡΠ΄Π΅Ρ ΠΏΡΠΈ ΠΏΡΠΈΠ³ΠΎΡΡΠ²Π°Π½Π½Ρ Ρ
ΡΠΎΠΌΠΎΡΠΎΠΌΠ½ΠΈΡ
ΠΏΡΠ΅ΠΏΠ°ΡΠ°ΡΡΠ² ΡΠΎΠΌΠ°ΡΠΈΡΠ½ΠΈΡ
ΠΊΠ»ΡΡΠΈΠ½ Π»ΡΠ΄ΠΈΠ½ΠΈ.ΠΡΠ΅Π΄ΡΡΠ°Π²Π»Π΅Π½ ΠΌΠ΅ΡΠΎΠ΄ ΠΏΠΎΡΡΡΠΎΠ΅Π½ΠΈΡ Π΄Π²ΡΡ
ΠΌΠ΅ΡΠ½ΡΡ
(2D) ΠΈ ΡΡΠ΅Ρ
ΠΌΠ΅ΡΠ½ΡΡ
(3D) ΠΏΡΠΎΡΠΈΠ»Π΅ΠΉ ΠΈΠ½ΡΠ΅Π½ΡΠΈΠ²Π½ΠΎΡΡΠΈ ΡΠΈΠ³Π½Π°Π»ΠΎΠ² ΡΠ»ΡΠΎΡΠ΅ΡΡΠ΅Π½ΡΠ½ΠΎΠΉ Π³ΠΈΠ±ΡΠΈΠ΄ΠΈΠ·Π°ΡΠΈΠΈ in situ (FISH), ΠΎΡΠ½ΠΎΠ²Π°Π½Π½ΡΠΉ Π½Π° ΠΊΠΎΠ»ΠΈΡΠ΅ΡΡΠ²Π΅Π½Π½ΠΎΠΉ FISH. ΠΠ°ΡΡΠΎΡΡΠ°Ρ ΠΌΠ΅ΡΠΎΠ΄ΠΈΠΊΠ° Π±ΡΠ»Π° ΠΈΡΠΏΠΎΠ»ΡΠ·ΠΎΠ²Π°Π½Π° Π΄Π»Ρ Π°Π½Π°Π»ΠΈΠ·Π° ΡΠ°ΡΠΏΠΎΠ»ΠΎΠΆΠ΅Π½ΠΈΡ ΠΈ ΡΠ°ΡΠΏΡΠ΅Π΄Π΅Π»Π΅Π½ΠΈΡ ΡΠΈΠ³Π½Π°Π»ΠΎΠ² Π² ΠΈΠ½ΡΠ΅ΡΡΠ°Π·Π½ΡΡ
ΡΠ΄ΡΠ°Ρ
ΠΊΠ»Π΅ΡΠΎΠΊ ΡΠ°Π·Π»ΠΈΡΠ½ΡΡ
ΡΠΎΠΌΠ°ΡΠΈΡΠ΅ΡΠΊΠΈΡ
ΡΠΊΠ°Π½Π΅ΠΉ ΡΠ΅Π»ΠΎΠ²Π΅ΠΊΠ°. ΠΡΠΏΠΎΠ»ΡΠ·ΠΎΠ²Π°Π½ΠΈΠ΅ 2D ΠΏΡΠΎΡΠΈΠ»Π΅ΠΉ ΠΈΠ½ΡΠ΅Π½ΡΠΈΠ²Π½ΠΎΡΡΠΈ ΠΏΡΠΎΠ΄Π΅ΠΌΠΎΠ½ΡΡΡΠΈΡΠΎΠ²Π°Π»ΠΎ Π²ΠΎΠ·ΠΌΠΎΠΆΠ½ΠΎΡΡΡ ΠΎΠΏΡΠ΅Π΄Π΅Π»Π΅Π½ΠΈΡ ΠΊΠΎΠ»ΠΎΠΊΠ°Π»ΠΈΠ·Π°ΡΠΈΠΈ FISH-ΡΠΈΠ³Π½Π°Π»ΠΎΠ². ΠΠΎΠ»Π΅Π΅ ΡΠΎΠ³ΠΎ, ΠΏΡΠ΅Π΄Π»ΠΎΠΆΠ΅Π½Π½ΡΠΉ ΠΏΠΎΠ΄Ρ
ΠΎΠ΄ ΠΏΠΎΠ·Π²ΠΎΠ»ΠΈΠ» ΠΈΠ΄Π΅Π½ΡΠΈΡΠΈΡΠΈΡΠΎΠ²Π°ΡΡ ΡΠ΅ΠΏΠ»ΠΈΡΠΈΡΠΎΠ²Π°Π½Π½ΡΠ΅ ΡΠΈΠ³Π½Π°Π»Ρ, Π΄Π°ΡΡ ΠΎΡΠ΅Π½ΠΊΡ ΡΡΡΠ΅ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ Π³ΠΈΠ±ΡΠΈΠ΄ΠΈΠ·Π°ΡΠΈΠΈ ΠΈ ΡΡΠ°Π²Π½ΠΈΡΠ΅Π»ΡΠ½ΡΠΉ Π°Π½Π°Π»ΠΈΠ· Π²Π°ΡΠΈΠ°ΡΠΈΠΈ ΡΠΎΠ΄Π΅ΡΠΆΠ°Π½ΠΈΡ ΠΠΠ ΡΠΏΠ΅ΡΠΈΡΠΈΡΠ΅ΡΠΊΠΈΡ
ΡΡΠ°ΡΡΠΊΠΎΠ² Ρ
ΡΠΎΠΌΠΎΡΠΎΠΌ. ΠΠΎΡΡΡΠΎΠ΅Π½ΠΈΠ΅ 3D ΠΏΡΠΎΡΠΈΠ»Π΅ΠΉ ΠΏΠΎΠΊΠ°Π·Π°Π»ΠΎ ΡΠ°ΡΠΏΡΠ΅Π΄Π΅Π»Π΅Π½ΠΈΠ΅ ΠΈΠ½ΡΠ΅Π½ΡΠΈΠ²Π½ΠΎΡΡΠΈ Π² ΠΏΡΠ΅Π΄Π΅Π»Π°Ρ
ΠΏΠ»ΠΎΡΠ°Π΄ΠΈ ΡΠΈΠ³Π½Π°Π»Π°. ΠΡΠΈΠΌΠ΅Π½Π΅Π½ΠΈΠ΅ ΡΡΠΎΠΉ ΠΌΠ΅ΡΠΎΠ΄ΠΈΠΊΠΈ ΠΏΠΎΠ·Π²ΠΎΠ»ΠΈΠ»ΠΎ ΠΎΠΏΡΠ΅Π΄Π΅Π»ΠΈΡΡ ΡΠΎΡΡΠ΅Π΄ΠΎΡΠΎΡΠ΅Π½ΠΈΠ΅ ΡΠ°Π·Π»ΠΈΡΠ½ΡΡ
ΡΠΈΠΏΠΎΠ² ΠΏΠΎΡΠ»Π΅Π΄ΠΎΠ²Π°ΡΠ΅Π»ΡΠ½ΠΎΡΡΠ΅ΠΉ ΠΠΠ: ΠΊΠ»Π°ΡΡΠΈΡΠ΅ΡΠΊΠ°Ρ ΡΠ°ΡΠ΅Π»Π»ΠΈΡΠ½Π°Ρ ΠΈ Π°Π»ΡΡΠΎΠΈΠ΄Π½Π°Ρ ΠΠΠ; Π³Π΅Π½Π½ΠΎΠ½Π°ΡΡΡΠ΅Π½Π½ΡΠ΅ (G-ΠΏΠΎΠ»ΠΎΠΆΠΈΡΠ΅Π»ΡΠ½ΡΠ΅ ΠΏΠΎΠ»ΠΎΡΡ) ΠΈ Π³Π΅Π½Π½ΠΎΠ½Π΅Π½Π°ΡΡΡΠ΅Π½Π½ΡΠ΅ (G-ΠΎΡΡΠΈΡΠ°ΡΠ΅Π»ΡΠ½ΡΠ΅ ΠΏΠΎΠ»ΠΎΡΡ) ΡΡΠ°ΡΡΠΊΠΈ Ρ
ΡΠΎΠΌΠΎΡΠΎΠΌ. ΠΡΠΎΠΌΠ΅ ΡΠΎΠ³ΠΎ, ΠΌΠ΅ΡΠΎΠ΄ΠΈΠΊΠ° Π΄Π°Π»Π° Π²ΠΎΠ·ΠΌΠΎΠΆΠ½ΠΎΡΡΡ ΠΎΡΠ΅Π½ΠΈΡΡ ΡΠ°ΡΠΏΠΎΠ»ΠΎΠΆΠ΅Π½ΠΈΠ΅ Ρ
ΡΠΎΠΌΠ°ΡΠΈΠ½Π° Π² ΠΈΠ½ΡΠ΅ΡΡΠ°Π·Π½ΡΡ
ΡΠ΄ΡΠ°Ρ
ΠΊΠ°ΠΊ ΠΊΡΠ»ΡΡΠΈΠ²ΠΈΡΠΎΠ²Π°Π½Π½ΡΡ
, ΡΠ°ΠΊ ΠΈ Π½Π΅ΠΊΡΠ»ΡΡΠΈΠ²ΠΈΡΠΎΠ²Π°Π½Π½ΡΡ
ΠΊΠ»Π΅ΡΠΎΠΊ. Π ΡΠ΅Π·ΡΠ»ΡΡΠ°ΡΠ΅ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡ Π±ΡΠ» ΡΠ΄Π΅Π»Π°Π½ Π²ΡΠ²ΠΎΠ΄ ΠΎ ΡΠΎΠΌ, ΡΡΠΎ ΠΏΡΠ΅Π΄Π»Π°Π³Π°Π΅ΠΌΡΠΉ ΠΏΠΎΠ΄Ρ
ΠΎΠ΄ ΡΠ²Π»ΡΠ΅ΡΡΡ ΡΡΡΠ΅ΠΊΡΠΈΠ²Π½ΠΎΠΉ Π΄ΠΎΠΏΠΎΠ»Π½ΠΈΡΠ΅Π»ΡΠ½ΠΎΠΉ ΠΌΠ΅ΡΠΎΠ΄ΠΈΠΊΠΎΠΉ Π΄Π»Ρ ΠΈΠ·ΡΡΠ΅Π½ΠΈΡ ΡΠ΄Π΅ΡΠ½ΠΎΠΉ ΠΎΡΠ³Π°Π½ΠΈΠ·Π°ΡΠΈΠΈ, ΡΠΏΠ΅ΡΠΈΡΠΈΠΊΠΈ Π²Π°ΡΠΈΠ°ΡΠΈΠΈ ΠΈ ΡΠ°ΡΠΏΠΎΠ»ΠΎΠΆΠ΅Π½ΠΈΡ ΠΏΠΎΡΠ»Π΅Π΄ΠΎΠ²Π°ΡΠ΅Π»ΡΠ½ΠΎΡΡΠ΅ΠΉ ΠΠΠ Π² ΠΈΠ½ΡΠ΅ΡΡΠ°Π·Π½ΡΡ
ΡΠ΄ΡΠ°Ρ
, Π° ΡΠ°ΠΊΠΆΠ΅ ΠΏΠΎΠ²Π΅Π΄Π΅- Π½ΠΈΡ ΡΠ΄Π΅Ρ ΠΏΡΠΈ ΠΏΡΠΈΠ³ΠΎΡΠΎΠ²Π»Π΅Π½ΠΈΠΈ Ρ
ΡΠΎΠΌΠΎΡΠΎΠΌΠ½ΡΡ
ΠΏΡΠ΅ΠΏΠ°ΡΠ°ΡΠΎΠ² ΡΠΎΠΌΠ°ΡΠΈΡΠ΅ΡΠΊΠΈΡ
ΠΊΠ»Π΅ΡΠΎΠΊ ΡΠ΅Π»ΠΎΠ²Π΅ΠΊΠ°
Fluorescence intensity profiles of in situ hybridization signals depict genome architecture within human interphase nuclei
Pericentric inversion inv(7)(p11q21.1): report on two cases and genotype-phenotype correlations
We report on two unrelated cases of pericentric inversion 46,XY,inv(7)(p11q21.1) associated with distinct pattern of malformation including mental retardation, development delay, ectrodactyly, facial dismorphism, high arched palate. Additionally, one case was found to be characterized by mesodermal dysplasia. Cytogenetic analysis of the families indicated that one case was a paternally inherited inversion whereas another case was a maternally inherited one. Molecular cytogenetic studies have shown paternal inversion to have a breakpoint within centromeric heterochromatin being the cause of alphoid DNA loss. Maternal inversion was also associated with a breakpoint within centromeric heterochromatin as well as inverted euchromatic chromosome region flanked by two disrupted alphoid DNA blocks.ΠΠΏΠΈΡΠ°Π½Ρ Π΄Π²Π° Π½Π΅ΡΠΎΠ΄ΡΡΠ²Π΅Π½Π½ΡΡ
ΡΠ»ΡΡΠ°Ρ ΠΏΠ΅ΡΠΈΡΠ΅Π½ΡΡΠΈΡΠ΅ΡΠΊΠΎΠΉ ΠΈΠ½Π²Π΅ΡΡΠΈΠΈ 46,XY,inv(7)(p11q21.1), ΡΠ²ΡΠ·Π°Π½Π½ΠΎΠΉ Ρ ΡΠΌΡΡΠ²Π΅Π½Π½ΠΎΠΉ ΠΎΡΡΡΠ°Π»ΠΎΡΡΡΡ, Π·Π°Π΄Π΅ΡΠΆΠΊΠΎΠΉ ΡΠ°Π·Π²ΠΈΡΠΈΡ, ΡΠΊΡΡΠΎΠ΄Π°ΠΊΡΠΈΠ»ΠΈΠ΅ΠΉ, Π°Π½ΠΎΠΌΠ°Π»ΠΈΡΠΌΠΈ Π»ΠΈΡΠ°, Π³ΠΎΡΠΈΡΠ΅ΡΠΊΠΈΠΌ Π½Π΅Π±ΠΎΠΌ. ΠΠΎΠΌΠΈΠΌΠΎ ΡΡΠΎΠ³ΠΎ, Π² ΠΎΠ΄Π½ΠΎΠΌ ΡΠ»ΡΡΠ°Π΅ Π½Π°Π±Π»ΡΠ΄Π°Π»ΠΈ ΠΌΠ΅Π·ΠΎΠ΄Π΅ΡΠΌΠ°Π»ΡΠ½ΡΡ Π΄ΠΈΡΠΏΠ»Π°Π·ΠΈΡ. Π¦ΠΈΡΠΎΠ³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΈΠΉ Π°Π½Π°Π»ΠΈΠ· ΡΠ΅ΠΌΠ΅ΠΉ ΠΏΠΎΠΊΠ°Π·Π°Π», ΡΡΠΎ Π² ΠΎΠ΄Π½ΠΎΠΌ ΡΠ»ΡΡΠ°Π΅ ΠΈΠ½Π²Π΅ΡΡΠΈΡ ΠΈΠΌΠ΅Π»Π° ΠΎΡΡΠΎΠ²ΡΠΊΠΎΠ΅ ΠΏΡΠΎΠΈΡΡ
ΠΎΠΆΠ΄Π΅Π½ΠΈΠ΅, Π² Π΄ΡΡΠ³ΠΎΠΌ β ΠΌΠ°ΡΠ΅ΡΠΈΠ½ΡΠΊΠΎΠ΅. Π‘ ΠΏΠΎΠΌΠΎΡΡΡ ΠΌΠΎΠ»Π΅ΠΊΡΠ»ΡΡΠ½ΠΎ-ΡΠΈΡΠΎΠ³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΈΡ
ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠΉ Π±ΡΠ»ΠΎ ΠΎΠΏΡΠ΅Π΄Π΅Π»Π΅Π½ΠΎ, ΡΡΠΎ ΡΠΎΡΠΊΠ° ΡΠ°Π·ΡΡΠ²Π° ΠΈΠ½Π²Π΅ΡΡΠΈΠΈ ΠΎΡΡΠΎΠ²ΡΠΊΠΎΠ³ΠΎ ΠΏΡΠΎΠΈΡΡ
ΠΎΠΆΠ΄Π΅Π½ΠΈΡ Π»ΠΎΠΊΠ°Π»ΠΈΠ·ΠΎΠ²Π°Π½Π° Π² ΡΠ΅Π½ΡΡΠΎΠΌΠ΅ΡΠ½ΠΎΠΌ Π³Π΅ΡΠ΅ΡΠΎΡ
ΡΠΎΠΌΠ°ΡΠΈΠ½Π΅ ΠΈ ΡΠ²ΡΠ·Π°Π½Π° Ρ ΠΏΠΎΡΠ΅ΡΠ΅ΠΉ Π°Π»ΡΡΠΎΠΈΠ΄Π½ΠΎΠΉ ΠΠΠ. ΠΡΠΈ Π°Π½Π°Π»ΠΈΠ·Π΅ ΠΈΠ½Π²Π΅ΡΡΠΈΠΈ ΠΌΠ°ΡΠ΅ΡΠΈΠ½ΡΠΊΠΎΠ³ΠΎ ΠΏΡΠΎΠΈΡΡ
ΠΎΠΆΠ΄Π΅Π½ΠΈΡ Π±ΡΠ»ΠΎ ΠΏΠΎΠΊΠ°Π·Π°Π½ΠΎ, ΡΡΠΎ ΡΠΎΡΠΊΠΈ ΡΠ°Π·ΡΡΠ²Π° ΡΠ°ΠΊΠΆΠ΅ Π»ΠΎΠΊΠ°Π»ΠΈΠ·ΠΎΠ²Π°Π½Ρ Π² ΡΠ΅Π½ΡΡΠΎΠΌΠ΅ΡΠ½ΠΎΠΌ Π³Π΅ΡΠ΅ΡΠΎΡ
ΡΠΎΠΌΠ°ΡΠΈΠ½Π΅ ΠΈ ΡΡΡ
ΡΠΎΠΌΠ°ΡΠΈΠ½Π΅ ΡΡΠ°ΡΡΠΊΠ° 7q21βq22, Π° ΡΠ°ΠΊΠΆΠ΅ ΠΈΠ²Π΅ΡΡΠΈΡΠΎΠ²Π°Π½Π½ΡΠΉ ΡΡΡ
ΡΠΎΠΌΠ°ΡΠΈΠ½ΠΎΠ²ΡΠΉ ΡΡΠ°ΡΡΠΎΠΊ ΡΠ°ΡΠΏΠΎΠ»ΠΎΠΆΠ΅Π½ ΠΌΠ΅ΠΆΠ΄Ρ Π΄Π²ΡΠΌΡ ΠΏΠ΅ΡΠ΅ΡΡΡΠΎΠ΅Π½Π½ΡΠΌΠΈ Π±Π»ΠΎΠΊΠ°ΠΌΠΈ Π°Π»ΡΡΠΎΠΈΠ΄Π½ΠΎΠΉ ΠΠΠ
Chimerism and multiple numerical chromosome imbalances in a spontaneously aborted fetus
We report on a case of chimerism and multiple abnormalities of chromosomes 21, X and Y in spontaneous abortion specimen. To the best our knowledge the present case is the first documented chimera in a spontaneously aborted fetus. The application of interphase fluorescence in situ hybridization (FISH) using chromosome enumeration and site-specific DNA probes showed trisomy X in 92 nuclei (23 %), tetrasomy X in 100 nuclei (25 %), pentasomy of chromosome X in 40 nuclei (10 %), XXY in 36 nuclei (9 %), XXXXXXYY in 12 nuclei (3 %), XXXXXYYYYY in 8 nuclei (2 %), trisomy 21 and female chromosome complement in 40 nuclei (10 %), normal female chromosome complement in 72 nuclei (18 %) out of 400 nuclei scored. Our experience indicates that the frequency of chimerism coupled with multiple chromosome abnormalities should be no less than 1 : 400 among spontaneous abortions. The difficulties of chimerism identification in fetal tissues are discussed
Non-disjunction of chromosome 21, alphoid DNA variation, and sociogenetic features of Down syndrome
The analysis of non-disjunction of chromosome 21 and alphoid DNA variation by using cytogenetic and molecular cytogenetic techniques (quantitative fluorescence in situ hybridization) in 74 nuclear families was performed. The establishment of possible correlation between alphoid DNA variation, parental age, environmental effects, and non-disjunction of chromosome 21 was made. The efficiency of techniques applied was found to be 92 % (68 from 74 cases). Maternal non-disjunction was found in 58 cases (86 %) and paternal non-disjunction β in 7 cases (10 %). Post-zygotic mitotic non-disjunction was determined in 2 cases (3 %) and one case was associated with Robertsonian translocation 46,XX,der(21;21)(q10;q10),+21. Maternal meiosis I errors were found in 43 cases (64 %) and maternal meiosis II errors β in 15 cases (22 %). Paternal meiosis I errors occurred in 2 cases (3 %) and paternal meiosis I errors β in 5 cases (7 %). The lack of the correlation between alphoid DNA variation and non-disjunction of chromosome 21 was established. Sociogenetic analysis revealed the association of intensive drug therapy of infectious diseases during the periconceptual period and maternal meiotic non-disjunction of chromosome 21. The correlation between non-disjunction of chromosome 21 and increased parental age as well as exposure to irradiation, alcohol, tobacco, mutagenic substances was not found. The possible relevance of data obtained to the subsequent studies of chromosome 21 non-disjunction is discussed.ΠΡΠΎΠ²Π΅Π΄Π΅Π½ Π°Π½Π°Π»ΠΈΠ· Π½Π΅ΡΠ°ΡΡ
ΠΎΠΆΠ΄Π΅Π½ΠΈΡ Ρ
ΡΠΎΠΌΠΎΡΠΎΠΌΡ 21 ΠΈ Π²Π°ΡΠΈΠ°ΡΠΈΠΈ Π°Π»ΡΡΠΎΠΈΠ΄Π½ΠΎΠΉ ΠΠΠ Π² 74 ΡΠ΄Π΅ΡΠ½ΡΡ
ΡΠ΅ΠΌΡΡΡ
Ρ Π΄Π΅ΡΡΠΌΠΈ, ΡΡΡΠ°Π΄Π°ΡΡΠΈΠΌΠΈ ΡΠΈΠ½Π΄ΡΠΎΠΌΠΎΠΌ ΠΠ°ΡΠ½Π°, Ρ ΠΏΠΎΠΌΠΎΡΡΡ ΡΠΈΡΠΎΠ³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΈΡ
ΠΈ ΠΌΠΎΠ»Π΅ΠΊΡΠ»ΡΡΠ½ΠΎ-ΡΠΈΡΠΎΠ³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΈΡ
(ΠΊΠΎΠ»ΠΈΡΠ΅ΡΡΠ²Π΅Π½Π½Π°Ρ ΡΠ»ΡΠΎΡΠ΅ΡΡΠ΅Π½ΡΠ½Π°Ρ Π³ΠΈΠ±ΠΈΠ΄ΠΈΠ·Π°ΡΠΈΡ in situ) ΠΌΠ΅ΡΠΎΠ΄ΠΎΠ². ΠΠΎΠΌΠΈΠΌΠΎ ΡΡΠΎΠ³ΠΎ, Π±ΡΠ» ΡΠ°ΠΊΠΆΠ΅ ΠΏΡΠΎΠ²Π΅Π΄Π΅Π½ Π°Π½Π°Π»ΠΈΠ· ΠΊΠΎΡΡΠ΅Π»ΡΡΠΈΠΈ ΠΌΠ΅ΠΆΠ΄Ρ Π²Π°ΡΠΈΠ°ΡΠΈΠ΅ΠΉ Π°Π»ΡΡΠΎΠΈΠ΄Π½ΠΎΠΉ ΠΠΠ, Π²ΠΎΠ·ΡΠ°ΡΡΠΎΠΌ ΡΠΎΠ΄ΠΈΡΠ΅Π»Π΅ΠΉ, ΡΠ°ΠΊΡΠΎΡΠ°ΠΌΠΈ ΠΎΠΊΡΡΠΆΠ°ΡΡΠ΅ΠΉ ΡΡΠ΅Π΄Ρ ΠΈ Π½Π΅ΡΠ°ΡΡ
ΠΎΠΆΠ΄Π΅Π½ΠΈΠ΅ΠΌ Ρ
ΡΠΎΠΌΠΎΡΠΎΠΌΡ 21. ΠΡΡΠ΅ΠΊΡΠΈΠ²Π½ΠΎΡΡΡ ΠΈΡΠΏΠΎΠ»ΡΠ·ΠΎΠ²Π°Π½Π½ΡΡ
ΠΌΠ΅ΡΠΎΠ΄ΠΎΠ² ΡΠΎΡΡΠ°Π²ΠΈΠ»Π° 92 % (68 ΠΈΠ· 74 ΡΠ»ΡΡΠ°Π΅Π²). ΠΠ°ΡΠ΅ΡΠΈΠ½ΡΠΊΠΎΠ΅ Π½Π΅ΡΠ°ΡΡ
ΠΎΠΆΠ΄Π΅Π½ΠΈΠ΅ Π±ΡΠ»ΠΎ ΠΎΠ±Π½Π°ΡΡΠΆΠ΅Π½ΠΎ Π² 58 ΡΠ»ΡΡΠ°ΡΡ
(86 %), ΠΎΡΡΠΎΠ²ΡΠΊΠΎΠ΅ β Π² 7 ΡΠ»ΡΡΠ°ΡΡ
(10 %). ΠΠΎΡΡΠ·ΠΈΠ³ΠΎΡΠΈΡΠ΅ΡΠΊΠΎΠ΅ ΠΌΠΈΡΠΎΡΠΈΡΠ΅ΡΠΊΠΎΠ΅ Π½Π΅ΡΠ°ΡΡ
ΠΎΠΆΠ΄Π΅Π½ΠΈΠ΅ Π±ΡΠ»ΠΎ ΠΎΠΏΡΠ΅Π΄Π΅Π»Π΅Π½ΠΎ Π² 2 ΡΠ»ΡΡΠ°ΡΡ
(3 %) ΠΈ Π² ΠΎΠ΄Π½ΠΎΠΌ ΡΠ»ΡΡΠ°Π΅ β ΡΠΎΠ±Π΅ΡΡΡΠΎΠ½ΠΎΠ²ΡΠΊΠ°Ρ ΡΡΠ°Π½ΡΠ»ΠΎΠΊΠ°ΡΠΈΡ 46,XX,der(21;21)(q10;q10),+21. ΠΡΠΈΠ±ΠΊΠΈ Π² ΠΌΠ°ΡΠ΅ΡΠΈΠ½ΡΠΊΠΎΠΌ ΠΌΠ΅ΠΉΠΎΠ·Π΅ I Π±ΡΠ»ΠΈ ΠΎΠ±Π½Π°ΡΡΠΆΠ΅Π½Ρ Π² 43 ΡΠ»ΡΡΠ°ΡΡ
(64 %), Π² ΠΌΠ°ΡΠ΅ΡΠΈΠ½ΡΠΊΠΎΠΌ ΠΌΠ΅ΠΉΠΎΠ·Π΅ II β Π² 15 ΡΠ»ΡΡΠ°ΡΡ
(22 %). ΠΡΠΈΠ±ΠΊΠΈ Π² ΠΎΡΡΠΎΠ²ΡΠΊΠΎΠΌ ΠΌΠ΅ΠΉΠΎΠ·Π΅ I Π±ΡΠ»ΠΈ ΠΎΠΏΡΠ΅Π΄Π΅Π»Π΅Π½Ρ Π² 2 ΡΠ»ΡΡΠ°ΡΡ
(2 %), Π² ΠΎΡΡΠΎΠ²ΡΠΊΠΎΠΌ ΠΌΠ΅ΠΉΠΎΠ·Π΅ II β Π² 5 ΡΠ»ΡΡΠ°ΡΡ
(7 %). ΠΡΠ»ΠΎ ΡΡΡΠ°Π½ΠΎΠ²Π»Π΅Π½ΠΎ ΠΎΡΡΡΡΡΡΠ²ΠΈΠ΅ ΠΊΠΎΡΡΠ΅Π»ΡΡΠΈΠΈ ΠΌΠ΅ΠΆΠ΄Ρ Π²Π°ΡΠΈΠ°ΡΠΈΠ΅ΠΉ Π°Π»ΡΡΠΎΠΈΠ΄Π½ΠΎΠΉ ΠΠΠ ΠΈ Π½Π΅ΡΠ°ΡΡ
ΠΎΠΆΠ΄Π΅Π½ΠΈΠ΅ΠΌ Ρ
ΡΠΎΠΌΠΎΡΠΎΠΌΡ 21. Π‘ΠΎΡΠΈΠΎΠ³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΈΠΉ Π°Π½Π°Π»ΠΈΠ· ΠΏΠΎΠΊΠ°Π·Π°Π» Π½Π°Π»ΠΈΡΠΈΠ΅ ΠΊΠΎΡΡΠ΅Π»ΡΡΠΈΠΈ ΠΌΠ΅ΠΆΠ΄Ρ ΠΈΠ½ΡΠ΅Π½ΡΠΈΠ²Π½ΠΎΠΉ Π»Π΅ΠΊΠ°ΡΡΡΠ²Π΅Π½Π½ΠΎΠΉ ΡΠ΅ΡΠ°ΠΏΠΈΠ΅ΠΉ ΠΈΠ½ΡΠ΅ΠΊΡΠΈΠΎΠ½Π½ΡΡ
Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΠΉ Π² ΠΏΠ΅ΡΠΈΠΊΠΎΠ½ΡΠ΅ΠΏΡΠΈΠΎΠ½Π½ΠΎΠΌ ΠΏΠ΅ΡΠΈΠΎΠ΄Π΅ ΠΈ Π½Π΅ΡΠ°ΡΡ
ΠΎΠΆΠ΄Π΅Π½ΠΈΠ΅ΠΌ Ρ
ΡΠΎΠΌΠΎΡΠΎΠΌΡ 21 Π² ΠΌΠ°ΡΠ΅ΡΠΈΠ½ΡΠΊΠΎΠΌ ΠΌΠ΅ΠΉΠΎΠ·Π΅. ΠΠΎΠΊΠ°Π·Π°Π½ΠΎ ΡΠ°ΠΊΠΆΠ΅, ΡΡΠΎ Π½Π΅ΡΠ°ΡΡ
ΠΎΠΆΠ΄Π΅Π½ΠΈΠ΅ Ρ
ΡΠΎΠΌΠΎΡΠΎΠΌΡ 21 Π½Π΅Π»ΡΠ·Ρ ΠΎΠΏΡΠ΅Π΄Π΅Π»ΠΈΡΡ Π΄ΠΎΡΡΠΎΠ²Π΅ΡΠ½ΠΎ ΡΠ²ΡΠ·Π°Π½Π½ΡΠΌ Ρ Π±ΠΎΠ»ΡΡΠΈΠΌ Π²ΠΎΠ·ΡΠ°ΡΡΠΎΠΌ ΡΠΎΠ΄ΠΈΡΠ΅Π»Π΅ΠΉ, Π²ΠΎΠ·Π΄Π΅ΠΉΡΡΠ²ΠΈΠ΅ΠΌ ΡΠ°Π΄ΠΈΠ°ΡΠΈΠΈ, ΡΠΏΠΎΡΡΠ΅Π±Π»Π΅Π½ΠΈΠ΅ΠΌ Π°Π»ΠΊΠΎΠ³ΠΎΠ»Ρ, ΠΊΡΡΠ΅Π½ΠΈΠ΅ΠΌ ΡΠ°Π±Π°ΠΊΠ°, Π° ΡΠ°ΠΊΠΆΠ΅ Π²ΠΎΠ·Π΄Π΅ΠΉΡΡΠ²ΠΈΠ΅ΠΌ Ρ
ΠΈΠΌΠΈΡΠ΅ΡΠΊΠΈΡ
ΡΠΎΠ΅Π΄ΠΈΠ½Π΅Π½ΠΈΠΉ Ρ ΠΌΡΡΠ°Π³Π΅Π½Π½ΡΠΌ ΡΡΡΠ΅ΠΊΡΠΎΠΌ. ΠΠ±ΡΡΠΆΠ΄Π°Π΅ΡΡΡ Π·Π½Π°ΡΠΈΠΌΠΎΡΡΡ ΠΏΠΎΠ»ΡΡΠ΅Π½Π½ΡΡ
ΡΠ΅Π·ΡΠ»ΡΡΠ°ΡΠΎΠ² Π΄Π»Ρ ΠΏΠΎΡΠ»Π΅Π΄ΡΡΡΠΈΡ
ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠΉ Π½Π΅ΡΠ°ΡΡ
ΠΎΠΆΠ΄Π΅Π½ΠΈΡ Ρ
ΡΠΎΠΌΠΎΡΠΎΠΌΡ 21