DNA Deoxyribonucleic acid (; DNA) is a polymer composed of two polynucleotide chains that coil around each other to form a double helix. The polymer carries genetic instructions for the development, functioning, growth and reproduction of al ...

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 * the segment is maximal, that is, it is delimited at both ends by ancestral recombination events.

Theory

All individuals in a finite population are related if traced back long enough and will, therefore, share segments of their

genomes A genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding genes, other functional regions of the genome such as ...

IBD. During

meiosis Meiosis () is a special type of cell division of germ cells in sexually-reproducing organisms that produces the gametes, the sperm or egg cells. It involves two rounds of division that ultimately result in four cells, each with only one c ...

segments of IBD are broken up by recombination. Therefore, the expected length of an IBD segment depends on the number of generations since the

most recent common ancestor A most recent common ancestor (MRCA), also known as a last common ancestor (LCA), is the most recent individual from which all organisms of a set are inferred to have descended. The most recent common ancestor of a higher taxon is generally assu ...

at the locus of the segment. The length of IBD segments that result from a common ancestor ''n'' generations in the past (therefore involving 2''n'' meiosis) is exponentially distributed with mean 1/(2''n'') Morgans (M). The expected number of IBD segments decreases as the number of generations since the common ancestor at this locus increases. For a specific DNA segment, the probability of being IBD decreases as 2^−2''n'' since in each meiosis the probability of transmitting this segment is 1/2.

Applications

Identified IBD segments can be used for a wide range of purposes. As noted above the amount (length and number) of IBD sharing depends on the familial relationships between the tested individuals. Therefore, one application of IBD segment detection is to quantify relatedness. Measurement of relatedness can be used in

forensic genetics DNA profiling (also called DNA fingerprinting and genetic fingerprinting) is the process of determining an individual's deoxyribonucleic acid (DNA) characteristics. DNA analysis intended to identify a species, rather than an individual, is cal ...

, but can also increase information in

genetic linkage Genetic linkage is the tendency of Nucleic acid sequence, DNA sequences that are close together on a chromosome to be inherited together during the meiosis phase of sexual reproduction. Two Genetic marker, genetic markers that are physically near ...

mapping and help to decrease

bias Bias is a disproportionate weight ''in favor of'' or ''against'' an idea or thing, usually in a way that is inaccurate, closed-minded, prejudicial, or unfair. Biases can be innate or learned. People may develop biases for or against an individ ...

by undocumented relationships in standard association studies. Another application of IBD is genotype imputation and

haplotype A haplotype (haploid genotype) is a group of alleles in an organism that are inherited together from a single parent. Many organisms contain genetic material (DNA) which is inherited from two parents. Normally these organisms have their DNA orga ...

phase Phase or phases may refer to: Science *State of matter, or phase, one of the distinct forms in which matter can exist *Phase (matter), a region of space throughout which all physical properties are essentially uniform *Phase space, a mathematica ...

inference. Long shared segments of IBD, which are broken up by short regions may be indicative for phasing errors.

IBD mapping

IBD mapping is similar to linkage analysis, but can be performed without a known pedigree on a cohort of unrelated individuals. IBD mapping can be seen as a new form of association analysis that increases the

power Power may refer to: Common meanings * Power (physics), meaning "rate of doing work" ** Engine power, the power put out by an engine ** Electric power, a type of energy * Power (social and political), the ability to influence people or events Math ...

to map genes or genomic regions containing multiple rare disease susceptibility variants. Using simulated data, Browning and Thompson showed that IBD mapping has higher power than association testing when multiple rare variants within a gene contribute to disease susceptibility. Via IBD mapping, genome-wide significant regions in isolated populations as well as outbred populations were found while standard association tests failed. Houwen et al. used IBD sharing to identify the chromosomal location of a gene responsible for benign recurrent intrahepatic

cholestasis Cholestasis is a condition where the flow of bile from the liver to the duodenum is impaired. The two basic distinctions are: * obstructive type of cholestasis, where there is a mechanical blockage in the duct system that can occur from a gallston ...

in an isolated fishing population. Kenny et al. also used an isolated population to fine-map a signal found by a

genome-wide association study In genomics, a genome-wide association study (GWA study, or GWAS), is an observational study of a genome-wide set of Single-nucleotide polymorphism, genetic variants in different individuals to see if any variant is associated with a trait. GWA s ...

(GWAS) of plasma plant sterol (PPS) levels, a surrogate measure of cholesterol absorption from the intestine. Francks et al. was able to identify a potential susceptibility locus for

schizophrenia Schizophrenia () is a mental disorder characterized variously by hallucinations (typically, Auditory hallucination#Schizophrenia, hearing voices), delusions, thought disorder, disorganized thinking and behavior, and Reduced affect display, f ...

and

bipolar disorder Bipolar disorder (BD), previously known as manic depression, is a mental disorder characterized by periods of Depression (mood), depression and periods of abnormally elevated Mood (psychology), mood that each last from days to weeks, and in ...

with genotype data of case-control samples. Lin et al. found a genome-wide significant linkage signal in a dataset of

multiple sclerosis Multiple sclerosis (MS) is an autoimmune disease resulting in damage to myelinthe insulating covers of nerve cellsin the brain and spinal cord. As a demyelinating disease, MS disrupts the nervous system's ability to Action potential, transmit ...

patients. Letouzé et al. used IBD mapping to look for

founder mutation In population genetics, the founder effect is the loss of genetic variation that occurs when a new population is established by a very small number of individuals from a larger population. It was first fully outlined by Ernst Mayr in 1942, using ...

s in

cancer Cancer is a group of diseases involving Cell growth#Disorders, abnormal cell growth with the potential to Invasion (cancer), invade or Metastasis, spread to other parts of the body. These contrast with benign tumors, which do not spread. Po ...

samples.

IBD segment detected by HapFABIA in 1000Genomes

IBD in population genetics

Detection of

natural selection Natural selection is the differential survival and reproduction of individuals due to differences in phenotype. It is a key mechanism of evolution, the change in the Heredity, heritable traits characteristic of a population over generation ...

in the human genome is also possible via detected IBD segments. Selection will usually tend to increase the number of IBD segments among individuals in a population. By scanning for regions with excess IBD sharing, regions in the human genome that have been under strong, very recent selection can be identified. In addition to that, IBD segments can be useful for measuring and identifying other influences on population structure. Gusev et al. showed that IBD segments can be used with additional modeling to estimate demographic history including bottlenecks and admixture. Using similar models Palamara et al. and Carmi et al. reconstructed the demographic history of

Ashkenazi Jewish Ashkenazi Jews ( ; also known as Ashkenazic Jews or Ashkenazim) form a distinct subgroup of the Jewish diaspora, that Ethnogenesis, emerged in the Holy Roman Empire around the end of the first millennium Common era, CE. They traditionally spe ...

and Kenyan Maasai individuals. Botigué et al. investigated differences in African ancestry among European populations. Ralph and Coop used IBD detection to quantify the common ancestry of different European populations and Gravel et al. similarly tried to draw conclusions of the genetic history of populations in the Americas. Ringbauer et al. utilized geographic structure of IBD segments to estimate dispersal within Eastern Europe during the last centuries. Using the 1000 Genomes data Hochreiter found differences in IBD sharing between African, Asian and European populations as well as IBD segments that are shared with ancient genomes like the

Neanderthal Neanderthals ( ; ''Homo neanderthalensis'' or sometimes ''H. sapiens neanderthalensis'') are an extinction, extinct group of archaic humans who inhabited Europe and Western and Central Asia during the Middle Pleistocene, Middle to Late Plei ...

or Denisova.

Methods and software

Programs for the detection of IBD segments in unrelated individuals:
RAPID
Ultra-fast Identity by Descent Detection in Biobank-Scale Cohorts using Positional Burrows–Wheeler Transform Naseri A, Liu X, Zhang S, Zhi D. Ultra-fast Identity by Descent Detection in Biobank-Scale Cohorts using Positional Burrows–Wheeler Transform BioRxiv 2017.
Parente
identifies IBD segments between pairs of individuals in unphased genotype dataRodriguez JM, Batzoglou S, Bercovici S. An accurate method for inferring relatedness in large datasets of unphased genotypes via an embedded likelihood-ratio test. RECOMB 2013, LNBI 7821:212-229.

finds segments of IBD between pairs of individuals in genome-wide SNP data
BEAGLE/RefinedIBD
finds IBD segments in pairs of individuals using a hashing method and evaluates their significance via a likelihood ratio

detects pairwise IBD segments in sequencing data
GERMLINE
discovers in linear-time IBD segments in pairs of individuals
DASH
builds upon pairwise IBD segments to infer clusters of individuals likely to be sharing a single haplotype
PLINK
is a tool set for whole genome association and population-based linkage analyses including a method for pairwise IBD segment detection
Relate
estimates the probability of IBD between pairs of individuals at a specific locus using SNPs
MCMC_IBDfinder
is based on

Markov chain Monte Carlo In statistics, Markov chain Monte Carlo (MCMC) is a class of algorithms used to draw samples from a probability distribution. Given a probability distribution, one can construct a Markov chain whose elements' distribution approximates it – that ...

(MCMC) for finding IBD segments in multiple individuals
IBD-Groupon
detects group-wise IBD segments based on pairwise IBD relationships
HapFABIA
identifies very short IBD segments characterized by rare variants in large

sequencing In genetics and biochemistry, sequencing means to determine the primary structure (sometimes incorrectly called the primary sequence) of an unbranched biopolymer. Sequencing results in a symbolic linear depiction known as a sequence which succ ...

data simultaneously in multiple individuals

References