Duplication of chickendefensin7gene generated by gene conversion and homologous recombination

Defensins constitute an evolutionary conserved family of cationic antimicrobial peptides that play a key role in host innate immune responses to infection. Defensin genes generally reside in complex genomic regions that are prone to structural variation, and defensin genes exhibit extensive copy number variation in humans and in other species. Copy number variation of defensin genes was examined in inbred lines of Leghorn and Fayoumi chickens, and a duplication ofdefensin7was discovered in the Fayoumi breed. Analysis of junction sequences confirmed the occurrence of a simple tandem duplication ofdefensin7with sequence identity at the junction, suggesting nonallelic homologous recombination betweendefensin7anddefensin6. The duplication event generated two chimeric promoters that are best explained by gene conversion followed by homologous recombination. Expression ofdefensin7was not elevated in animals with two genes despite both genes being transcribed in the tissues examined. Computational prediction of promoter regions revealed the presence of several putative transcription factor binding sites generated by the duplication event. These data provide insight into the evolution and possible function of large gene families and specifically, the defensins.

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Inferring Homologous Recombination Deficiency of Ovarian Cancer From the Landscape of Copy Number Variation at Subchromosomal and Genetic Resolutions

Frontiers in Oncology ◽

10.3389/fonc.2021.772604 ◽

2021 ◽

Vol 11 ◽

Author(s):

Meng Zhang ◽

Si-Cong Ma ◽

Jia-Le Tan ◽

Jian Wang ◽

Xue Bai ◽

...

Keyword(s):

Ovarian Cancer ◽

Homologous Recombination ◽

Copy Number Variation ◽

Copy Number ◽

The Cancer Genome Atlas ◽

Homologous Recombination Deficiency ◽

Number Variation ◽

Cancer Genome Atlas ◽

Tumor Types ◽

Pan Cancer

BackgroundHomologous recombination deficiency (HRD) is characterized by overall genomic instability and has emerged as an indispensable therapeutic target across various tumor types, particularly in ovarian cancer (OV). Unfortunately, current detection assays are far from perfect for identifying every HRD patient. The purpose of this study was to infer HRD from the landscape of copy number variation (CNV).MethodsGenome-wide CNV landscape was measured in OV patients from the Australian Ovarian Cancer Study (AOCS) clinical cohort and >10,000 patients across 33 tumor types from The Cancer Genome Atlas (TCGA). HRD-predictive CNVs at subchromosomal resolution were identified through exploratory analysis depicting the CNV landscape of HRD versus non-HRD OV patients and independently validated using TCGA and AOCS cohorts. Gene-level CNVs were further analyzed to explore their potential predictive significance for HRD across tumor types at genetic resolution.ResultsAt subchromosomal resolution, 8q24.2 amplification and 5q13.2 deletion were predominantly witnessed in HRD patients (both p < 0.0001), whereas 19q12 amplification occurred mainly in non-HRD patients (p < 0.0001), compared with their corresponding counterparts within TCGA-OV. The predictive significance of 8q24.2 amplification (p < 0.0001), 5q13.2 deletion (p = 0.0056), and 19q12 amplification (p = 0.0034) was externally validated within AOCS. Remarkably, pan-cancer analysis confirmed a cross-tumor predictive role of 8q24.2 amplification for HRD (p < 0.0001). Further analysis of CNV in 8q24.2 at genetic resolution revealed that amplifications of the oncogenes, MYC (p = 0.0001) and NDRG1 (p = 0.0004), located on this fragment were also associated with HRD in a pan-cancer manner.ConclusionsThe CNV landscape serves as a generalized predictor of HRD in cancer patients not limited to OV. The detection of CNV at subchromosomal or genetic resolution could aid in the personalized treatment of HRD patients.

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High levels of copy number variation of ampliconic genes across major human Y haplogroups

10.1101/230342 ◽

2017 ◽

Author(s):

Danling Ye ◽

Arslan Zaidi ◽

Marta Tomaszkiewicz ◽

Corey Liebowitz ◽

Michael DeGiorgio ◽

...

Keyword(s):

Copy Number Variation ◽

Y Chromosome ◽

Copy Number ◽

Gene Copy Number ◽

Gene Families ◽

Digital Pcr ◽

Gene Copy ◽

Copy Numbers ◽

Number Variation ◽

Gene Copy Numbers

AbstractDue to its highly repetitive nature, the human male-specific Y chromosome remains understudied. It is important to investigate variation on the Y chromosome to understand its evolution and contribution to phenotypic variation, including infertility. Approximately 20% of the human Y chromosome consists of ampliconic regions which include nine multi-copy gene families. These gene families are expressed exclusively in testes and usually implicated in spermatogenesis. Here, to gain a better understanding of the role of the Y chromosome in human evolution and in determining sexually dimorphic traits, we studied ampliconic gene copy number variation in 100 males representing ten major Y haplogroups world-wide. Copy number was estimated with droplet digital PCR. In contrast to low nucleotide diversity observed on the Y in previous studies, here we show that ampliconic gene copy number diversity is very high. A total of 98 copy-number-based haplotypes were observed among 100 individuals, and haplotypes were sometimes shared by males from very different haplogroups, suggesting homoplasies. The resulting haplotypes did not cluster according to major Y haplogroups. Overall, only three gene families (DATZ, RBMY, TSPY) showed significant differences in copy number among major Y haplogroups, and the haplogroup of an individual could not be predicted based on his ampliconic gene copy numbers. Finally, we found a significant correlation between copy number variation and individual’s height (for three gene families), but not between the former and facial masculinity/femininity. Our results suggest rapid evolution of ampliconic gene copy numbers on the human Y, and we discuss its causes.

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