Mathematical Analysis of Copy Number Variation in a DNA Sample Using Digital PCR on a Nanofluidic Device

Hybrid zones have long been described as "windows on the evolutionary process", and studying them has become even more important since the advance in the genome analysis tools. The hybrid zone between two subspecies of the house mouse (Mus musculus musculus and Mus m. domesticus) is a unique model speciation system to study fine scale interactions of recently diverged genomes. Here, we explore the role of gene Copy Number Variation in shaping the barrier to introgression in the hybrid zone within a previously established transect in Central Europe. The CNV of seven pre-selected candidate genes was determined via droplet-digital PCR and analyzed in the context of ~500k SNPs, with the ancestral population (i.e. musculus or domesticus) of every SNP allele previously inferred in the admixed individuals (Baird et al., in prep.). The copy numbers of five genes were clearly associated with the prevalence of either musculus or domesticus genomes across the hybrid zone. In three cases, the highest and/or outlying levels of association were observed at or very close to the annotated positions of the respective gene amplicons, demonstrating the power of our approach in confirming the reference locations of copy number variants. Notably, several other reference locations were recognized as positive outliers in the association with particular CNV genes, possibly representing the extra gene copies and/or their epistatic interaction sites.

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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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Abstract P2-03-04: Application of digital-PCR technology to determine c-MET copy number variation in paired primary breast cancer and brain metastases

10.1158/1538-7445.sabcs16-p2-03-04 ◽

2017 ◽

Cited By ~ 1

Author(s):

A Giannoudis ◽

R Zakaria ◽

A Platt-Higgins ◽

KAR Syed ◽

K Ashton ◽

...

Keyword(s):

Breast Cancer ◽

Brain Metastases ◽

Copy Number Variation ◽

Primary Breast Cancer ◽

Copy Number ◽

Digital Pcr ◽

Number Variation ◽

Pcr Technology

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AMY2B Gene Copy-Number Variation Studied by Droplet Digital PCR (ddPCR) in Three Canids: Red Fox, Arctic Fox, and Chinese Raccoon Dog

Folia Biologica ◽

10.3409/fb_68-2.07 ◽

2020 ◽

Vol 68 (2) ◽

pp. 51-55

Author(s):

Michal Antkowiak ◽

Joanna Nowacka-Woszuk ◽

Izabela Szczerbal ◽

Marek Switonski ◽

Maciej Szydlowski

Keyword(s):

Copy Number Variation ◽

Copy Number ◽

Red Fox ◽

Digital Pcr ◽

The Arctic ◽

Raccoon Dog ◽

Red Foxes ◽

Arctic Foxes ◽

Number Variation ◽

Raccoon Dogs

Copy-number variation (CNV) is an important source of genetic variation, and one that played a role in the process of domestication. The adaptation to a new diet is a characteristic feature of dog domestication. We therefore sought genomic signatures of this process. The pancreatic alpha-amylase gene (AMY2B), expressed in the pancreas, exhibits a variable number of copies. It has been shown that the multiplication of this gene is associated with the adaptation of dogs to a starch-rich diet. To date, there has been no information made available on the copy-number variation of AMY2B in canid farm animals. The aim of the present study was to examine the AMY2B copy number in the red fox, the arctic fox, and in the Chinese raccoon dog. Droplet digital PCR (ddPCR) was used to count the gene copies in 152 animals (60 red foxes, 53 arctic foxes, and 39 Chinese raccoon dogs). We found that the majority (91%) of the animals had two copies of this gene. Of the red foxes and Chinese raccoon dogs, only 8% had three copies, while 32% of the arctic foxes had three copies. Our study showed that the multiplication of the AMY2B gene did not occur over several decades of breeding selection, which may reflect the low-starch feeding regime.

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