Runs of homozygosity

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Runs of homozygosity (ROH) are contiguous lengths of homozygous genotypes that are present in an individual due to parents transmitting identical haplotypes to their offspring. [1]

The potential of predicting or estimating individual autozygosity for a subpopulation is the proportion of the autosomal genome above a specified length, termed Froh. [2]

A research study in UK Biobank, All of Us and Million Veteran Program found that FROH declines over time. [3]

Usage

This technique can be used to identify the genomic footprint of inbreeding in conservation programs, as organisms that have undergone recent inbreeding will exhibit long runs of homozygosity. For example, the step-wise reintroduction strategy of the Alpine Ibex in the Swiss Alps created several strong population bottlenecks that reduced the genetic diversity of the newly introduced individuals. The effect of inbreeding in the resulting sub-populations could be studied by measuring the runs of homozygosity in different individuals. [4]

In clinical laboratory testing, the detection of ROH in itself does not indicate a particular genetic disorder but indicates an increased risk of autosomal recessive inherited diseases. [5] As ROHs smaller than 3 Mb spread throughout the genome are common even in outbred populations, [6] these segments were usually thought to not be important enough to report. [5] Large ROH can be indicative of uniparental isodisomy [7] with follow-up testing to rule out false positives, there is currently no consistent reporting standards among different laboratories. [5]

ROH can be used to detect the possibility of incest in humans. [8] [5]

Related Research Articles

<span class="mw-page-title-main">Inbreeding</span> Reproduction by closely related organisms

Inbreeding is the production of offspring from the mating or breeding of individuals or organisms that are closely related genetically. By analogy, the term is used in human reproduction, but more commonly refers to the genetic disorders and other consequences that may arise from expression of deleterious recessive traits resulting from incestuous sexual relationships and consanguinity. Animals avoid inbreeding only rarely.

<span class="mw-page-title-main">Uniparental disomy</span> Medical condition

Uniparental disomy (UPD) occurs when a person receives two copies of a chromosome, or of part of a chromosome, from one parent and no copy from the other. UPD can be the result of heterodisomy, in which a pair of non-identical chromosomes are inherited from one parent or isodisomy, in which a single chromosome from one parent is duplicated. Uniparental disomy may have clinical relevance for several reasons. For example, either isodisomy or heterodisomy can disrupt parent-specific genomic imprinting, resulting in imprinting disorders. Additionally, isodisomy leads to large blocks of homozygosity, which may lead to the uncovering of recessive genes, a similar phenomenon seen in inbred children of consanguineous partners.

<span class="mw-page-title-main">Consanguinity</span> Property of being from the same kinship as another person

Consanguinity is the characteristic of having a kinship with a relative who is descended from a common ancestor.

<span class="mw-page-title-main">Single-nucleotide polymorphism</span> Single nucleotide in genomic DNA at which different sequence alternatives exist

In genetics and bioinformatics, a single-nucleotide polymorphism is a germline substitution of a single nucleotide at a specific position in the genome. Although certain definitions require the substitution to be present in a sufficiently large fraction of the population, many publications do not apply such a frequency threshold.

The coefficient of relationship is a measure of the degree of consanguinity between two individuals. The term coefficient of relationship was defined by Sewall Wright in 1922, and was derived from his definition of the coefficient of inbreeding of 1921. The measure is most commonly used in genetics and genealogy. A coefficient of inbreeding can be calculated for an individual, and is typically one-half the coefficient of relationship between the parents.

In population genetics, F-statistics describe the statistically expected level of heterozygosity in a population; more specifically the expected degree of (usually) a reduction in heterozygosity when compared to Hardy–Weinberg expectation.

<span class="mw-page-title-main">Overdominance</span>

Overdominance is a phenomenon in genetics where the phenotype of the heterozygote lies outside the phenotypical range of both homozygous parents. Overdominance can also be described as heterozygote advantage regulated by a single genomic locus, wherein heterozygous individuals have a higher fitness than homozygous individuals. However, not all cases of the heterozygote advantage are considered overdominance, as they may be regulated by multiple genomic regions. Overdominance has been hypothesized as an underlying cause for heterosis.

<span class="mw-page-title-main">Identity by descent</span> Identical nucleotide sequence due to inheritance without recombination from a common ancestor

A DNA segment is identical by state (IBS) in two or more individuals if they have identical nucleotide sequences in this segment. An IBS segment is identical by descent (IBD) in two or more individuals if they have inherited it from a common ancestor without recombination, that is, the segment has the same ancestral origin in these individuals. DNA segments that are IBD are IBS per definition, but segments that are not IBD can still be IBS due to the same mutations in different individuals or recombinations that do not alter the segment.

Genetic load is the difference between the fitness of an average genotype in a population and the fitness of some reference genotype, which may be either the best present in a population, or may be the theoretically optimal genotype. The average individual taken from a population with a low genetic load will generally, when grown in the same conditions, have more surviving offspring than the average individual from a population with a high genetic load. Genetic load can also be seen as reduced fitness at the population level compared to what the population would have if all individuals had the reference high-fitness genotype. High genetic load may put a population in danger of extinction.

Inbreeding depression is the reduced biological fitness that has the potential to result from inbreeding. The loss of genetic diversity that is seen due to inbreeding, results from small population size. Biological fitness refers to an organism's ability to survive and perpetuate its genetic material. Inbreeding depression is often the result of a population bottleneck. In general, the higher the genetic variation or gene pool within a breeding population, the less likely it is to suffer from inbreeding depression, though inbreeding and outbreeding depression can simultaneously occur.

<span class="mw-page-title-main">Thelytoky</span> Type of parthenogenesis in which females are produced from unfertilized eggs

Thelytoky is a type of parthenogenesis and is the absence of mating and subsequent production of all female diploid offspring as for example in aphids. Thelytokous parthenogenesis is rare among animals and reported in about 1,500 species, about 1 in 1000 of described animal species, according to a 1984 study. It is more common in invertebrates, like arthropods, but it can occur in vertebrates, including salamanders, fish, and reptiles such as some whiptail lizards.

In molecular biology, SNP array is a type of DNA microarray which is used to detect polymorphisms within a population. A single nucleotide polymorphism (SNP), a variation at a single site in DNA, is the most frequent type of variation in the genome. Around 335 million SNPs have been identified in the human genome, 15 million of which are present at frequencies of 1% or higher across different populations worldwide.

<span class="mw-page-title-main">Genome-wide association study</span> Study of genetic variants in different individuals

In genomics, a genome-wide association study, is an observational study of a genome-wide set of genetic variants in different individuals to see if any variant is associated with a trait. GWA studies typically focus on associations between single-nucleotide polymorphisms (SNPs) and traits like major human diseases, but can equally be applied to any other genetic variants and any other organisms.

<span class="mw-page-title-main">Zygosity</span> Degree of similarity of the alleles in an organism

Zygosity is the degree to which both copies of a chromosome or gene have the same genetic sequence. In other words, it is the degree of similarity of the alleles in an organism.

Disease gene identification is a process by which scientists identify the mutant genotypes responsible for an inherited genetic disorder. Mutations in these genes can include single nucleotide substitutions, single nucleotide additions/deletions, deletion of the entire gene, and other genetic abnormalities.

<span class="mw-page-title-main">Jalili syndrome</span> Medical condition

Jalili syndrome is a genetic disorder characterized by the combination of cone-rod dystrophy of the retina and amelogenesis imperfecta. It was characterized in 1988 by Dr. I. K. Jalili and Dr. N. J. D. Smith, following the examination of 29 members of an inbred Arab family living within the Gaza Strip.

<span class="mw-page-title-main">Synaptotagmin-14</span> Protein-coding gene in the species Homo sapiens

Synaptotagmin XIV is a protein that in humans is encoded by the SYT14 gene.

Genetic studies on Arabs refers to the analyses of the genetics of ethnic Arab people in the Middle East and North Africa and parts of Sub-Sahara Africa where Black Arabs claim descent. Arabs are genetically diverse as a result of their intermarriage and mixing with indigenous people of the pre-Islamic Middle East and North Africa following the Arab and Islamic expansion. Genetic ancestry components related to the Arabian Peninsula display an increasing frequency pattern from west to east over North Africa. A similar frequency pattern exist across northeastern Africa with decreasing genetic affinities to groups of the Arabian Peninsula along the Nile river valley across Sudan and the more they go south. This genetic cline of admixture is dated to the time of Arab expansion and immigration to North Africa (Maghreb) and northeast Africa.

Arthur L. Beaudet is an American physician. He is a past professor and chair of molecular and human genetics at Baylor College of Medicine. He was inducted into the Institute of Medicine in 1995, the Society of Scholars in 2008 and into the National Academy of Sciences in 2011.

Elective genetic and genomic testing are DNA tests performed for an individual who does not have an indication for testing. An elective genetic test analyzes selected sites in the human genome while an elective genomic test analyzes the entire human genome. Some elective genetic and genomic tests require a physician to order the test to ensure that individuals understand the risks and benefits of testing as well as the results. Other DNA-based tests, such as a genealogical DNA test do not require a physician's order. Elective testing is generally not paid for by health insurance companies. With the advent of personalized medicine, also called precision medicine, an increasing number of individuals are undertaking elective genetic and genomic testing.

References

  1. ↑ Purfield DC, Berry DP, McParland S, Bradley DG (August 2012). "Runs of homozygosity and population history in cattle". BMC Genetics. 13: 70. doi: 10.1186/1471-2156-13-70 . PMC   3502433 . PMID   22888858.
  2. ↑ McQuillan R, Leutenegger AL, Abdel-Rahman R, Franklin CS, Pericic M, Barac-Lauc L, et al. (September 2008). "Runs of homozygosity in European populations". American Journal of Human Genetics. 83 (3): 359–72. doi:10.1016/j.ajhg.2008.08.007. PMC   2556426 . PMID   18760389.
  3. ↑ Colbert, Sarah M.C.; Wendt, Frank R.; Pathak, Gita A.; Helmer, Drew A.; Hauser, Elizabeth R.; Keller, Matthew C.; Polimanti, Renato; Johnson, Emma C. (2023-06-01). "Declining autozygosity over time: An exploration in over 1 million individuals from three diverse cohorts". The American Journal of Human Genetics. 110 (6): 1008–1014. doi:10.1016/j.ajhg.2023.04.007. PMC   10257001 . PMID   37178685 – via Elsevier Science Direct.
  4. ↑ Grossen C, Biebach I, Angelone- Alasaad S, Keller LF, Croll D (2018). "Population genomics analyses of European ibex species show lower diversity and higher inbreeding in reintroduced populations Evol Appl. 2018;11: 123–139". Evolutionary Applications. 11 (2): 123–139. doi:10.1111/eva.12490. PMC   5775499 . PMID   29387150.
  5. 1 2 3 4 Gonzales, Patrick R.; Andersen, Erica F.; Brown, Teneille R.; Horner, Vanessa L.; Horwitz, Juli; Rehder, Catherine W.; Rudy, Natasha L.; Robin, Nathaniel H.; Thorland, Erik C.; on behalf of the ACMG Laboratory Quality Assurance Committee (2022-02-03). "Interpretation and reporting of large regions of homozygosity and suspected consanguinity/uniparental disomy, 2021 revision: A technical standard of the American College of Medical Genetics and Genomics (ACMG)". Genetics in Medicine. 24 (2): 255–261. doi: 10.1016/j.gim.2021.10.004 .
  6. ↑ Ceballos, Francisco C.; Joshi, Peter K.; Clark, David W.; Ramsay, Michèle; Wilson, James F. (2018-04-15). "Runs of homozygosity: windows into population history and trait architecture". Nature Reviews Genetics. 19 (4): 220–234. doi:10.1038/nrg.2017.109. hdl: 20.500.11820/1928cc4c-af43-489f-b743-52ae374412d7 . ISSN   1471-0056.
  7. ↑ Papenhausen, Peter; Schwartz, Stuart; Risheg, Hiba; Keitges, Elisabeth; Gadi, Inder; Burnside, Rachel D.; Jaswaney, Vikram; Pappas, John; Pasion, Romela; Friedman, Kenneth; Tepperberg, James (2011-04-15). "UPD detection using homozygosity profiling with a SNP genotyping microarray". American Journal of Medical Genetics Part A. 155 (4): 757–768. doi:10.1002/ajmg.a.33939.
  8. ↑ Zhang, Sarah (18 March 2024). "DNA Tests Are Uncovering the True Prevalence of Incest". The Atlantic. Retrieved 12 May 2024.
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