What is hardy weinberg equilibrium

Figure 3. Impact of tandem repeats, segmental duplications and allele balance on the probability of variant deviation from Hardy-Weinberg Equilibrium HWE due to heterozygote excess HetExc. For each variant these statistics are aggregated into a single metric that represents cumulative percentage of Variant Carriers with Normal 0. Secondly, to investigate the correlation between HetExc and Allele Balance AB , which is a known indicator of systematic genotyping errors Muyas et al.

In gnomAD, variant AB data is stored as a number of variant carriers converted to percentages here in 20 AB groupings from 0 to 1, 0. For an average variant, the majority of variant carriers Only 2. These HetExc variants were then compared with a group of variants that survived the same filtering process, but did not have an excess of heterozygotes HetExc-. The HetExc- and HetExc groups consisted of 39, and variants 50, and if counted in seven ethnic populations separately, Figure 4A in 11, and genes, respectively.

Figure 4. B Proportions of missense, synonymous and other protein coding variants in HetExc and HetExc- datasets. C ClinVar status e. To determine which of the HetExc candidate recessive disease causing variants were already known, their clinical significance in the disease variant database ClinVar; Landrum et al. HetExc variant enrichment in known AR genes adds evidence that some of the selected variants might deviate from HWE due to natural selection and could have some disease association.

Since gnomAD v3 mostly consisted of individuals that were not present in gnomAD v2. However, our findings that HetDef is a major cause of deviations from HWE in all populations is contrary to previous studies Chen et al. However, previous studies focused on error detection in older and smaller datasets, some of which were corrected in gnomAD.

Graffelman et al. We observed a higher rate of HetExc variants in these regions, as well as those that had low allele balance, which correlates with previous work Graffelman et al. Chen et al. However, this approach resulted in the exclusion of rare variants that were analyzed in this study and might be more affected by the Wahlund effect i. Moreover, some of the HetExc variants detected in previous studies were marked as non-pass quality or were no longer HetExc in gnomAD, possibly due to differences in variant filtering and genotype calling procedures.

For example, c. Another example, the BRSK2 variant c. Therefore, a higher rate of HetDef variants in our study could be explained by a larger population size and a different variant dataset, as well as improvements in variant filtering and genotype calling procedures. Analysis of HetExc variants Supplementary Table S1 , selected as recessive disease causing candidates, led to somewhat contradictory results, which should be interpreted with caution. Moreover, despite applying our extensive filtering strategies, many of the HetExc variants might still be deviating from HWE due to genotype errors or by chance due to insufficient population size.

However, the c. Therefore, the difference between the number of homozygote in gnomAD v2. Nevertheless, the presence of known pathogenic and heterozygote advantageous variants such as HBB c. Especially, the CHD6 gene variant c. Although CHD6 is not yet linked with any disease, it is known to act as transcriptional repressor of different viruses including influenza and papiloma virus Alfonso et al. Interestingly, c. We anticipate that improvements in sequencing technologies and variant filtering software should reduce the number of false positive HetExc variants in the future.

In fact, false positive HetExc variants that survived our strict quality filters, might aid the development of more efficient sequencing filtering strategies by helping to understand new patterns of genotype errors. Consequently, some common recessive disease causing variants were missed even if homozygous individuals were completely absent in the population.

For example, HetExc of the c. As the number of sequenced exomes and genomes is rapidly growing, this problem may soon be addressed. Indeed, the United Kingdom National Health Service is planning to sequence 1 million genomes in the next 4 years with a wider ambition to increase this number to 5 million 3.

Therefore, it might be possible to use HWE strategies to detect rare recessive disease causing variants in the near future. In this study, we explored the use of HWE to identify potential recessive disease causing variants in a large mainly healthy population database by developing a bespoke filtering strategy to detect variants where an excess of heterozygotes in a population could be a result of natural selection.

Overall, this approach showed potential, especially for the AFR population, successfully identifying some variants in recessive diseases that are known to be heterozygote advantageous, and providing novel candidates for further investigation. A natural progression of this work would be validation of genotype calls of HetExc variants to understand possible causes of genotype errors and analysis of the biological effect of true positive HetExc variants to determine their potential health implications.

Similarly, natural selection and nonrandom mating disrupt the Hardy-Weinberg equilibrium because they result in changes in gene frequencies. This occurs because certain alleles help or harm the reproductive success of the organisms that carry them. Another factor that can upset this equilibrium is genetic drift, which occurs when allele frequencies grow higher or lower by chance and typically takes place in small populations.

Gene flow, which occurs when breeding between two populations transfers new alleles into a population, can also alter the Hardy-Weinberg equilibrium. Because all of these disruptive forces commonly occur in nature, the Hardy-Weinberg equilibrium rarely applies in reality. In population genetics studies, the Hardy-Weinberg equation can be used to measure whether the observed genotype frequencies in a population differ from the frequencies predicted by the equation.

Hardy-Weinberg equation. Further Exploration Concept Links for further exploration allele frequency Hardy-Weinberg equilibrium allele genotype gene flow genetic drift natural selection evolution. Related Concepts 8. Log In Bookstore Join Renew. It looks like your browser does not have JavaScript enabled. Please turn on JavaScript and try again. Page Content.

The implications of the Hardy-Weinberg Law are that: The population is in a state of equilibrium. The frequencies of alleles in a population will remain constant from generation to generation.