Molecular methods for genotyping complex copy number polymorphisms

Optimization Algorithms for Identification and Genotyping of Copy Number Polymorphisms in Human Populations

Recent studies show that copy number polymorphisms (CNPs), defined as genome segments that are polymorphic with regard to genomic copy number and segregate at greater than 1% frequency in the populations, are associated with various diseases. Since rare copy number variations (CNVs) and CNPs bear different characteristics, the problem of discovering CNPs presents opportunities beyond what is av...

Methods for genotyping single nucleotide polymorphisms.

One of the fruits of the Human Genome Project is the discovery of millions of DNA sequence variants in the human genome. The majority of these variants are single nucleotide polymorphisms (SNPs). A dense set of SNP markers opens up the possibility of studying the genetic basis of complex diseases by population approaches. In all study designs, a large number of individuals must be genotyped wit...

Amplification ratio control system for copy number variation genotyping

We describe a generic design for ratiometric analysis suitable for determination of copy number variation (CNV) class of a gene. Following two initial sequence-specific PCR priming cycles, both ends of both amplicons (one test and one reference) in a duplex reaction, are all primed by the same universal primer (UP). Following each amplification denaturation step, the UP target and its reverse c...

Statistical methods for DNA copy-number detection

Copy number variation detection and genotyping from exome sequence data.

While exome sequencing is readily amenable to single-nucleotide variant discovery, the sparse and nonuniform nature of the exome capture reaction has hindered exome-based detection and characterization of genic copy number variation. We developed a novel method using singular value decomposition (SVD) normalization to discover rare genic copy number variants (CNVs) as well as genotype copy numb...