Group of genes from one parent
DNA molecule 1 differs from DNA molecule 2 at a single base-pair location (a C/A polymorphism).
A
haplotype
(
haploid
genotype
) is a group of
alleles
in an
organism
that are inherited together from a single parent.
[1]
[2]
Many organisms contain genetic material (
DNA
) which is inherited from two parents. Normally these organisms have their DNA organized in two sets of pairwise similar
chromosomes
. The offspring gets one chromosome in each pair from each parent. A set of pairs of chromosomes is called
diploid
and a set of only one half of each pair is called haploid. The haploid genotype (haplotype) is a genotype that considers the singular chromosomes rather than the pairs of chromosomes. It can be all the chromosomes from one of the parents or a minor part of a chromosome, for example a sequence of 9000
base pairs
or a small set of alleles.
Specific contiguous parts of the chromosome are likely to be inherited together and not be split by
chromosomal crossover
, a phenomenon called
genetic linkage
.
[3]
[4]
As a result, identifying these statistical associations and a few alleles of a specific haplotype sequence can facilitate identifying
all other such
polymorphic sites that are nearby on the chromosome (
imputation
).
[5]
Such information is critical for investigating the genetics of common
diseases
; which in fact have been investigated in humans by the
International HapMap Project
.
[6]
[7]
Other parts of the genome are almost always haploid and do not undergo crossover: for example, human
mitochondrial DNA
is passed down through the maternal line and the
Y chromosome
is passed down the paternal line. In these cases, the entire sequence can be grouped into a simple evolutionary tree, with each branch founded by a
unique-event polymorphism
mutation (often, but not always, a
single-nucleotide polymorphism
(SNP)). Each
clade
under a branch, containing haplotypes with a single shared ancestor, is called a
haplogroup
.
[8]
[9]
[10]
Haplotype resolution
[
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]
An organism's
genotype
may not define its haplotype uniquely. For example, consider a
diploid
organism and two bi-allelic
loci
(such as
SNPs
) on the same chromosome. Assume the first locus has alleles
A
or
T
and the second locus
G
or
C
. Both loci, then, have three possible
genotypes
: (
AA
,
AT
, and
TT
) and (
GG
,
GC
, and
CC
), respectively. For a given individual, there are nine possible configurations (haplotypes) at these two loci (shown in the
Punnett square
below). For individuals who are homozygous at one or both loci, the haplotypes are unambiguous - meaning that there is not any differentiation of haplotype T1T2 vs haplotype T2T1; where T1 and T2 are labeled to show that they are the same locus, but labeled as such to show it does not matter which order you consider them in, the end result is two T loci. For individuals
heterozygous
at both loci, the
gametic phase
is
ambiguous
- in these cases, an observer does not know which haplotype the individual has, e.g., TA vs AT.
Locus 1
Locus 2
|
AA
|
AT
|
TT
|
GG
|
AG AG
|
AG TG
|
TG TG
|
GC
|
AG AC
|
AG TC
or
AC TG
|
TG TC
|
CC
|
AC AC
|
AC TC
|
TC TC
|
The only unequivocal method of resolving phase ambiguity is by
sequencing
. However, it is possible to estimate the probability of a particular haplotype when phase is ambiguous using a sample of individuals.
Given the genotypes for a number of individuals, the haplotypes can be inferred by haplotype resolution or
haplotype phasing
techniques. These methods work by applying the observation that certain haplotypes are common in certain genomic regions. Therefore, given a set of possible haplotype resolutions, these methods choose those that use fewer different haplotypes overall. The specifics of these methods vary - some are based on combinatorial approaches (e.g.,
parsimony
), whereas others use likelihood functions based on different models and assumptions such as the
Hardy?Weinberg principle
, the
coalescent theory
model, or perfect phylogeny. The parameters in these models are then estimated using algorithms such as the
expectation-maximization algorithm
(EM),
Markov chain Monte Carlo
(MCMC), or
hidden Markov models
(HMM).
Microfluidic whole genome haplotyping
is a technique for the physical separation of individual chromosomes from a
metaphase
cell followed by direct resolution of the haplotype for each allele.
Gametic phase
[
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]
In
genetics
, a
gametic phase
represents the original allelic combinations that a
diploid
individual inherits from both parents.
[11]
It is therefore a particular association of
alleles
at different loci on the same
chromosome
. Gametic phase is influenced by
genetic linkage
.
[12]
Y-DNA haplotypes from genealogical DNA tests
[
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]
Unlike other chromosomes, Y chromosomes generally do not come in pairs. Every human male (excepting those with
XYY syndrome
) has only one copy of that chromosome. This means that there is not any chance variation of which copy is inherited, and also (for most of the chromosome) not any shuffling between copies by
recombination
; so, unlike
autosomal
haplotypes, there is effectively not any randomisation of the Y-chromosome haplotype between generations. A human male should largely share the same Y chromosome as his father, give or take a few mutations; thus Y chromosomes tend to pass largely intact from father to son,
with a small but accumulating number of mutations that can serve to differentiate male lineages.
In particular, the Y-DNA represented as the numbered results of a
Y-DNA genealogical DNA test
should match, except for mutations.
UEP results (SNP results)
[
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]
Unique-event polymorphisms
(UEPs) such as SNPs represent
haplogroups
. STRs represent haplotypes. The results that comprise the full Y-DNA haplotype from the Y chromosome DNA test can be divided into two parts: the results for UEPs, sometimes loosely called the SNP results as most UEPs are
single-nucleotide polymorphisms
, and the results for
microsatellite
short tandem repeat
sequences (
Y-STRs
).
The UEP results represent the inheritance of events it is believed can be assumed to have happened only once in all human history. These can be used to identify the individual's
Y-DNA haplogroup
, his place in the "family tree" of the whole of humanity. Different Y-DNA haplogroups identify genetic populations that are often distinctly associated with particular geographic regions; their appearance in more recent populations located in different regions represents the migrations tens of thousands of years ago of the direct
patrilineal
ancestors of current individuals.
Y-STR haplotypes
[
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]
Genetic results also include the
Y-STR haplotype
, the set of results from the Y-STR markers tested.
Unlike the UEPs, the Y-STRs mutate much more easily, which allows them to be used to distinguish recent genealogy. But it also means that, rather than the population of descendants of a genetic event all sharing the
same
result, the Y-STR haplotypes are likely to have spread apart, to form a
cluster
of more or less similar results. Typically, this cluster will have a definite most probable center, the
modal haplotype
(presumably similar to the haplotype of the original founding event), and also a
haplotype diversity
? the degree to which it has become spread out. The further in the past the defining event occurred, and the more that subsequent population growth occurred early, the greater the haplotype diversity will be for a particular number of descendants. However, if the haplotype diversity is smaller for a particular number of descendants, this may indicate a more recent common ancestor, or a recent population expansion.
It is important to note that, unlike for UEPs, two individuals with a similar Y-STR haplotype may not necessarily share a similar ancestry. Y-STR events are not unique. Instead, the clusters of Y-STR haplotype results inherited from different events and different histories tend to overlap.
In most cases, it is a long time since the haplogroups' defining events, so typically the cluster of Y-STR haplotype results associated with descendants of that event has become rather broad. These results will tend to significantly overlap the (similarly broad) clusters of Y-STR haplotypes associated with other haplogroups. This makes it impossible for researchers to predict with absolute certainty to which Y-DNA haplogroup a Y-STR haplotype would point. If the UEPs are not tested, the Y-STRs may be used only to predict probabilities for haplogroup ancestry, but not certainties.
A similar scenario exists in trying to evaluate whether shared surnames indicate shared genetic ancestry. A cluster of similar Y-STR haplotypes may indicate a shared common ancestor, with an identifiable modal haplotype, but only if the cluster is sufficiently distinct from what may have happened by chance from different individuals who historically adopted the same name independently. Many names were adopted from common occupations, for instance, or were associated with habitation of particular sites. More extensive haplotype typing is needed to establish genetic genealogy. Commercial DNA-testing companies now offer their customers testing of more numerous sets of markers to improve definition of their genetic ancestry. The number of sets of markers tested has increased from 12 during the early years to 111 more recently.
Establishing plausible relatedness between different surnames data-mined from a database is significantly more difficult. The researcher must establish that the
very nearest
member of the population in question, chosen purposely from the population for that reason, would be unlikely to match by accident. This is more than establishing that a
randomly selected
member of the population is unlikely to have such a close match by accident. Because of the difficulty, establishing relatedness between different surnames as in such a scenario is likely to be impossible, except in special cases where there is specific information to drastically limit the size of the population of candidates under consideration.
Diversity
[
edit
]
Haplotype diversity is a measure of the uniqueness of a particular haplotype in a given population. The haplotype diversity (H) is computed as:
[13]
![{\displaystyle H={\frac {N}{N-1}}(1-\sum _{i}x_{i}^{2})}](https://wikimedia.org/api/rest_v1/media/math/render/svg/50386edd32ca04b9892ebc4b893414dae0bd7e72)
where
![{\displaystyle x_{i}}](https://wikimedia.org/api/rest_v1/media/math/render/svg/e87000dd6142b81d041896a30fe58f0c3acb2158)
is the (relative) haplotype frequency of each haplotype in the sample and
![{\displaystyle N}](https://wikimedia.org/api/rest_v1/media/math/render/svg/f5e3890c981ae85503089652feb48b191b57aae3)
is the sample size. Haplotype diversity is given for each sample.
See also
[
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]
References
[
edit
]
- ^
By C. Barry Cox, Peter D. Moore, Richard Ladle. Wiley-Blackwell, 2016.
ISBN
978-1-118-96858-1
p106.
Biogeography: An Ecological and Evolutionary Approach
- ^
Editorial Board, V&S Publishers, 2012,
ISBN
9381588643
p137.
Concise Dictionary of Science
- ^
BiologyPages/H/Haplotypes.html Kimball's Biology Pages
(Creative Commons Attribution 3.0)
- ^
"haplotype / haplotypes | Learn Science at Scitable"
.
www.nature.com
.
- ^
Yoosefzadeh-Najafabadi, Mohsen; Rajcan, Istvan; Eskandari, Milad (2022).
"Optimizing genomic selection in soybean: An important improvement in agricultural genomics"
.
Heliyon
.
8
(11): e11873.
Bibcode
:
2022Heliy...811873Y
.
doi
:
10.1016/j.heliyon.2022.e11873
.
PMC
9713349
.
PMID
36468106
.
- ^
The International HapMap Consortium (2003).
"The International HapMap Project"
(PDF)
.
Nature
.
426
(6968): 789?796.
Bibcode
:
2003Natur.426..789G
.
doi
:
10.1038/nature02168
.
hdl
:
2027.42/62838
.
PMID
14685227
.
S2CID
4387110
.
- ^
The International HapMap Consortium (2005).
"A haplotype map of the human genome"
.
Nature
.
437
(7063): 1299?1320.
Bibcode
:
2005Natur.437.1299T
.
doi
:
10.1038/nature04226
.
PMC
1880871
.
PMID
16255080
.
– This article speaks of a
haplotype length
, which is the length of a contiguous run of the chromosome inherited from a single parent.
- ^
Arora, Devender; Singh, Ajeet; Sharma, Vikrant; Bhaduria, Harvendra Singh; Patel, Ram Bahadur (2015).
"Hgs
Db
: Haplogroups Database to understand migration and molecular risk assessment"
.
Bioinformation
.
11
(6): 272?5.
doi
:
10.6026/97320630011272
.
PMC
4512000
.
PMID
26229286
.
- ^
International Society of Genetic Genealogy 2015
Genetics Glossary
,
Haplogroup
- ^
"Facts & Genes. Volume 7, Issue 3"
. Archived from
the original
on May 9, 2008.
- ^
Taylor, Duncan; Bright, Jo-Anne; Buckleton, John S. (2016). "Biological basis for DNA evidence". In Buckleton, John S.; Bright, Jo-Anne; Taylor, Duncan (eds.).
Forensic DNA Evidence Interpretation
(2nd ed.). Boca Rotan, FL: CRC Press. pp. 1?36.
ISBN
9781482258899
.
- ^
Excoffier, Laurent (1 November 2003).
"Gametic phase estimation over large genomic regions using an adaptive window approach"
.
Human Genomics
.
1
(1): 7?19.
doi
:
10.1186/1479-7364-1-1-7
.
PMC
3525008
.
PMID
15601529
.
- ^
Masatoshi Nei and
Fumio Tajima
, "DNA polymorphism detectable by restriction endonucleases", Genetics 97:145 (1981)
External links
[
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]