Aoasm.ru

Медицинский портал
0 просмотров
Рейтинг статьи
1 звезда2 звезды3 звезды4 звезды5 звезд
Загрузка...

Можно ли вылечить синдром делеции 1q21.1 (OMIM: 612474)

Можно ли вылечить синдром делеции 1q21.1 (OMIM: 612474)

For a general phenotypic description and a discussion of genetic heterogeneity of neuroblastoma, see NBLST1 (256700).

Mapping

Diskin et al. (2009) described the identification of a common copy number variation (CNV) at chromosome 1q21.1 associated with neuroblastoma in a discovery set of 846 Caucasian patients with neuroblastoma and 803 controls. The findings were confirmed in 2 independent replication sets comprising 595 cases and 3,357 controls. They first observed a hemizygous approximately 300-kb deletion at 1q21.1 that occurred in 15.6% of cases but in only 9.1% of controls. The difference in hemizygous deletion frequency was significant at p = 1.83 x 10(-19). The observed frequency of homozygous deletion was the same in cases and controls (1.3% overall). The maximal deletion size was about 143 kb; within this region, Diskin et al. (2009) identified a novel gene, NBPF23 (612970).

Molecular Genetics

In an analysis of 18 neuroblastomas, both tumors and cell lines, of known copy number at 1q21.1, Diskin et al. (2009) observed a clear correlation between CNV state and NBPF23 transcript expression. Notably, 2-copy samples clustered into 2 distinct expression classes (p = 0.007), with low and higher expression respectively, and these were thought to represent different 1q21.1 CNV genotypes. There are 2 possible CNV genotypes for 2 copy samples, which the authors referred to as 2:0 (cis) and 1:1 (trans) based on the number of NBPF23 copies present on each chromosome in a diploid genome. Two neuroblastoma samples in the low expression group could be demonstrated to have originated from the 2:0 constitutional CNV genotype because they had somatically acquired a gain of chromosome 1q (3 copies of chromosome 1q), yet there were 2 copies of the gene with heterozygous SNPs. Diskin et al. (2009) proposed a model in which NBPF23 expression is decreased when 2 NBPF23 copies are in the cis configuration as opposed to the trans configuration. The findings implicated this gene in the early tumorigenesis of neuroblastoma.

Читать еще:  Можно ли создать семью троюродным братьям и сестрам
REFERENCES

Diskin, S. J., Hou, C., Glessner, J. T., Attiyeh, E. F., Laudenslager, M., Bosse, K., Cole, K., Mosse, Y. P., Wood, A., Lynch, J. E., Pecor, K., Diamond, M., and 15 others. Copy number variation at 1q21.1 associated with neuroblastoma. Nature 459: 987-991, 2009. [PubMed: 19536264, images, related citations] [Full Text]

% 613017

NEUROBLASTOMA, SUSCEPTIBILITY TO, 6; NBLST6

ORPHA: 635;

Cytogenetic location: 1q21.1 Genomic coordinates (GRCh38): 1:143,200,000-147,500,000

Gene-Phenotype Relationships
LocationPhenotypePhenotype
MIM number
InheritancePhenotype
mapping key
1q21.16130172
TEXT

For a general phenotypic description and a discussion of genetic heterogeneity of neuroblastoma, see NBLST1 (256700).

Mapping

Diskin et al. (2009) described the identification of a common copy number variation (CNV) at chromosome 1q21.1 associated with neuroblastoma in a discovery set of 846 Caucasian patients with neuroblastoma and 803 controls. The findings were confirmed in 2 independent replication sets comprising 595 cases and 3,357 controls. They first observed a hemizygous approximately 300-kb deletion at 1q21.1 that occurred in 15.6% of cases but in only 9.1% of controls. The difference in hemizygous deletion frequency was significant at p = 1.83 x 10(-19). The observed frequency of homozygous deletion was the same in cases and controls (1.3% overall). The maximal deletion size was about 143 kb; within this region, Diskin et al. (2009) identified a novel gene, NBPF23 (612970).

Molecular Genetics

In an analysis of 18 neuroblastomas, both tumors and cell lines, of known copy number at 1q21.1, Diskin et al. (2009) observed a clear correlation between CNV state and NBPF23 transcript expression. Notably, 2-copy samples clustered into 2 distinct expression classes (p = 0.007), with low and higher expression respectively, and these were thought to represent different 1q21.1 CNV genotypes. There are 2 possible CNV genotypes for 2 copy samples, which the authors referred to as 2:0 (cis) and 1:1 (trans) based on the number of NBPF23 copies present on each chromosome in a diploid genome. Two neuroblastoma samples in the low expression group could be demonstrated to have originated from the 2:0 constitutional CNV genotype because they had somatically acquired a gain of chromosome 1q (3 copies of chromosome 1q), yet there were 2 copies of the gene with heterozygous SNPs. Diskin et al. (2009) proposed a model in which NBPF23 expression is decreased when 2 NBPF23 copies are in the cis configuration as opposed to the trans configuration. The findings implicated this gene in the early tumorigenesis of neuroblastoma.

голоса
Рейтинг статьи
Ссылка на основную публикацию
ВсеИнструменты
Adblock
detector