Hardy-Weinberg equilibrium revisited for inferences on genotypes featuring allele and copy-number variations

  title={Hardy-Weinberg equilibrium revisited for inferences on genotypes featuring allele and copy-number variations},
  author={Andreas Recke and Klaus-G{\"u}nther Recke and Saleh M. Ibrahim and Steffen M{\"o}ller and Reinhard Vonthein},
  journal={Scientific Reports},
Copy number variations represent a substantial source of genetic variation and are associated with a plethora of physiological and pathophysiological conditions. Joint copy number and allelic variations (CNAVs) are difficult to analyze and require new strategies to unravel the properties of genotype distributions. We developed a Bayesian hidden Markov model (HMM) approach that allows dissecting intrinsic properties and metastructures of the distribution of CNAVs within populations, in… 
3 Citations

The transitivity of the Hardy-Weinberg law.

The transitivity of the Hardy-Weinberg law

Results of statistical tests for Hardy-Weinberg equilibrium obtained with polymorphisms that are reduced by deletion or joining of alleles are seen to be consistent with the formulated transitivity principle, and its usefulness in practical genetic data analysis with multi-allelic markers is explored.



Allele-specific copy number profiling by next-generation DNA sequencing

A new method, falcon, for finding somatic allele-specific copy number changes by next generation sequencing of tumors with matched normals, based on a change-point model on a bivariate mixed Binomial process, which explicitly models the copy numbers of the two chromosome haplotypes and corrects for local allele- specific coverage biases.

MOCSphaser: a haplotype inference tool from a mixture of copy number variation and single nucleotide polymorphism data

A new tool to infer population frequencies of such alleles and haplotypes from observed copy numbers and SNP genotypes, using the expectation-maximization algorithm is developed, which can also handle copy numbers ambiguously determined, such as 2 or 3 copies, due to experimental noise.

Allele-specific copy number analysis of tumors

A genome-wide map of allelic skewness in breast cancer is constructed, indicating loci where one allele is preferentially lost, whereas the other allele isPreferentially gained, and it is hypothesized that these alternative alleles have a different influence on breast carcinoma development.

Evidence for both copy number and allelic (NA1/NA2) risk at the FCGR3B locus in systemic lupus erythematosus

The results suggest that one mechanism by which CNV at this locus confers disease risk is directly as a result of reduced FcγRIIIb function, either because of reduced expression (related to CNV) orBecause of reduced affinity for its ligand (NA1/NA2 allotype).

Ontogenetic De Novo Copy Number Variations (CNVs) as a Source of Genetic Individuality: Studies on Two Families with MZD Twins for Schizophrenia

Genome-wide alterations in two nuclear families each with a pair of monozygotic twins discordant for schizophrenia evaluated by the Affymetrix 6.0 human SNP array are reported to argue for enduring genome-wide changes during cellular transmission.

Concurrent triplication and uniparental isodisomy: evidence for microhomology-mediated break-induced replication model for genomic rearrangements

Two cases with interstitial triplication followed by uniparental isodisomy (isoUPD) for remainder of the chromosomal arm are reported, representing the first detailed genomic analysis that provides support for a MMBIR mechanism inducing copy number gains and segmental isoUPD in tandem.

Copy number variation in autoimmunity — importance hidden in complexity?

The reasons for the lack of definitive data on CNV‐autoimmunity associations, as well as the technical challenges for the field are the focus of this review.

Copy number variation of the activating FCGR2C gene predisposes to idiopathic thrombocytopenic purpura.

It is proposed that the activating FCGR2C-ORF genotype predisposes to ITP by altering the balance of activating and inhibitory FcgammaR on immune cells.

Mechanisms of change in gene copy number

Current models of the mechanisms that cause copy number variation focus on perturbation of DNA replication and replication of non-contiguous DNA segments and cellular stress might induce repair of broken replication forks to switch from high-fidelity homologous recombination to non-homologous repair, thus promoting copy number change.