Download handedness - UNIT NAME

OMIM - *139900 HAND SKILL, RELATIVE; HSR
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*139900 HAND SKILL, RELATIVE; HSR
Alternative titles; symbols
HANDEDNESS
Gene map locus 2p12-q22
TEXT
Annett (1964) postulated that right-handedness is an incomplete dominant, or intermediate, i.e., that
dominant homozygotes are always right-handed with 'speech highly developed in the left hemisphere.'
Recessive homozygotes are consistently left-handed with speech in the right hemisphere. Heterozygotes
may use either hand and develop speech in either hemisphere. From twin studies, Rife (1940) had earlier
concluded that handedness is a multifactorial trait. Levy and Nagylaki (1972) reviewed experimental
data and theoretical work on the inheritance of handedness and cerebral dominance. They found that all
quantitative information was in excellent agreement with a 2-gene, 4-allele model, one locus pertaining
to left or right hemispheric dominance and the other to contralateral or ipsilateral hand control relative to
the dominant hemisphere. Hicks and Kinsbourne (1976) found that hand preference of college students
correlated significantly with the writing hand of their biologic parents but not with that of the
stepparents.
Huheey (1977) suggested that preferential right-handedness in man has its evolutionary origin in relation
to the tendency of human (and presumably prehuman) mothers to hold infants on the left side. The
practice has been ascribed to imprinting and a soothing effect of the sound of the mother's heartbeat on
the infant; thus, dextral mothers would be more skillful at manipulation of objects with the free hand and
would be selectively favored. Handedness appears to have remained about 93% right-handed over 5,000
years as indicated by a survey of art works (Coren and Porac, 1977).
Laland et al. (1995) presented a model of handedness that proposes that no genetic variation underlies
differences in handedness and that variation in handedness among humans is the result of a combination
of cultural and developmental factors, with a remaining genetic influence because handedness is a
facultative trait.
Klar (1996) presented a genetic model for human handedness that hypothesized the existence of a single
gene, designated RGHT (pronounced as right) by him, which confers right-handedness; individuals
lacking this gene, RGHT(-)/RGHT(-), display random handedness such that one-half are left-handed
(LH) and the other half are right-handed (RH). Tests of the hypothesis were presented using data from
Rife (1940). These data involved the families of 687 students attending Ohio State University.
Approximately half of the children of LH x LH families were LH and the remainder were RH.
Reference was also made to Lefthanders International and the organization's 'Lefthander' magazine,
which advertised the survey that was undertaken for these studies.
Geschwind et al. (2002) explored the relative contribution of environmental and genetic influence on
cerebral asymmetry by examining the volumes of left and right cerebral cortex in a large cohort of aging
identical and fraternal twins and investigated their relationship to handedness. Cerebral lobar volume
was found to have a major genetic component, indicating that genes play a large role in changes in brain
volume that occur with aging. Shared environment, which likely represents in utero events, had about
twice the effect on the left hemisphere as on the right, consistent with less genetic control over the left
hemisphere. To test the major genetic models of handedness and cerebral asymmetry, twin pairs were
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divided into those with 2 right handers and those with at least 1 left hander (nonright handers). Genetic
factors contributed twice the influence to left and right cerebral hemispheric volumes in right-handed
twin pairs, suggesting a large decrement in genetic control of cerebral volumes in the nonright-handed
twin pairs. This loss of genetic determination of left and right cerebral hemispheres in the nonrighthanded twin pairs is consistent with models postulating a right-hand/left-hemisphere-biasing genetic
influence, a 'right-shift' genotype that is lost in left handers, resulting in decreased cerebral asymmetry.
Bishop (2001) used data from 2 twin studies to address 2 related questions. First, is there any association
between handedness and specific speech and language impairment (SSLI) in children? Second, is there
genetic influence on individual differences in handedness, and, if so, are the same genes implicated in
the cause of SSLI? No handedness differences were found between 58 monozygotic and 26 dizygotic
pairs previously recruited for an investigation into the genetic origins of SSLI and singleton controls. To
investigate familial transmission of handedness, inventory data for parents and their twins were
combined. The most parsimonious model of the findings was one that accounted for parent-child
resemblance solely in terms of cultural transmission. Bishop (2001) concluded that, overall, there was
no evidence that genes play a role in determining stable individual differences in hand preference.
Handedness is a characteristic, obviously complex in its causation, that may prove amenable to analysis
of genetic contribution when a full gene map has been developed (Williamson, 1986). It is a behavioral
trait that may be a model for other behavioral traits, normal and abnormal. The observation that the
proportion of left-handers in populations decreases with age, diminishing from 13% in 20-year-olds to
less than 1% in 80-year-olds, led to the suggestion that sinistrality may be associated with decreased life
span. Reduced longevity in left-handers was also suggested by an archival study of records on 2,271
major-league baseball players (Halpern and Coren, 1988). In a questionnaire study of deceased persons
identified through death certificates, Halpern and Coren (1991) found significantly more left-handers
than right-handers among those who had died in accidents--a result consistent with earlier findings. Age
of death in general was lower in left-handers and mixed-handers than in right-handers of either sex.
Halpern and Coren (1991) stated that it is likely that the correlates of sinistrality, not sinistrality itself,
are responsible for the increased risk; left-handedness may indicate covert neuropathologic features.
Schur (1986) could not demonstrate the association between handedness and an autoimmune disease,
systemic lupus erythematosus (152700), which had been proposed by Geschwind and Behan (1982).
In southern Sweden, Olsson and Ingvar (1991) found that left-handedness was significantly less
common among patients with breast cancer (1.5%) than among a female referent population (5%); P less
than 0.0025. They interpreted the finding as support for theories suggesting that hormonal factors in
early life are important both for handedness and for the risk of breast cancer.
MAPPING
In a sample of 195 reading-disabled sib pairs in the United Kingdom, Francks et al. (2002) performed a
genomewide quantitative trait locus (QTL) linkage analysis using a continuous measure of relative hand
skill (PegQ) rather than treating handedness as a categorical state. A QTL on chromosome 2p12-p11.2
yielded strong evidence for linkage to PegQ and another suggestive QTL on 17p11-q23 was also
identified. Relative hand skill therefore appears to be a complex multifactorial phenotype with a
heterogeneous background, but nevertheless is amenable to QTL-based gene mapping approaches.
Francks et al. (2003) found evidence supporting their earlier location of a QTL for relative hand skill to
chromosome 2p12-q11 in a new sample of 105 pairs of adult brothers drawn from a sample of 168
unrelated male sibships (338 brothers) that was originally collected for investigating X-linked effects on
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handedness. The evidence of linkage had a P value of 0.00035, thus greatly exceeding significance
guidelines for confirmation of linkage (guideline P = 0.01, suggested by Lander and Kruglyak, 1995).
Francks et al. (2003) concluded that, although handedness variation may be etiologically complex, there
is at least 1 polymorphic genetic influence that is located on 2p12-q11.
HISTORY
Bodmer and McKie (1994) referred to the left-handedness of the Kerr family which gave rise to the
layout of a Kerr castle stronghold, Ferniehirst, on the border between England and Scotland. Whereas in
most castles staircases spiral clockwise, Ferniehirst has counterclockwise ones, providing left-handed
swordsmen with an advantage, the bends giving a defender's left hand freedom to move over the open
railing. The association between the Kerr name and left-handedness was such that throughout Scotland
the expression Kerr-handed, or kerry- or corry-fisted, is said to be commonly used to mean left-handed.
Bodmer and McKie (1994) quoted a survey of doctors who were asked to note the handedness of any
patient bearing the surname Kerr: 'a total of 29.5 percent of the Kerrs were reported, by both British and
North American doctors, to be 'left-handed or ambidextrous' compared with only 11% of a control
family.' Thus, in the Kerr family, there is still a strong majority of right handers. Furthermore, the lefthandedness may have been encouraged from the beginning. 'Andrew Kerr, founder of the family's
Ferniehirst dynasty in 1457, was certainly left-handed and found the characteristic a powerful asset in
battle.' It appears that he specifically taught his sons and armed men-servants (who, by custom, took the
family name) to wield sword and axe with the left hand, and they, in turn, did the same with their sons.
SEE ALSO
Annett (1979); Annett (1973); Annett (1978); Ferronato et al. (1974); Levy (1976); Springer and
Searleman (1978)
REFERENCES
1. Annett, M. :
Familial handedness in three generations predicted by the right shift theory. Ann. Hum.
Genet. 42: 479-491, 1979.
PubMed ID : 475335
2. Annett, M. :
A model of the inheritance of handedness and cerebral dominance. Nature 204: 59-60, 1964.
PubMed ID : 14240116
3. Annett, M. :
Handedness in families. Ann. Hum. Genet. 37: 93-105, 1973.
PubMed ID : 4759906
4. Annett, M. :
Genetic and nongenetic influences on handedness. Behav. Genet. 8: 227-249, 1978.
PubMed ID : 687316
5. Bishop, D. V. M. :
Individual differences in handedness and specific speech and language impairment:
evidence against a genetic link. Behav. Genet. 31: 339-351, 2001.
PubMed ID : 11720120
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6. Bodmer, W.; McKie, R. :
The Book of Man: the Quest to Discover Our Genetic Heritage. London: Little, Brown and
Co. (pub.) 1994. Pp. 1-5.
7. Coren, S.; Porac, C. :
Fifty centuries of right-handedness: the historic record. Science 198: 631-632, 1977.
PubMed ID : 335510
8. Ferronato, S.; Thomas, D.; Sadava, D. :
Preferences for handedness, arm folding, and hand clasping in families. Hum. Hered. 24:
345-351, 1974.
PubMed ID : 4461659
9. Francks, C.; DeLisi, L. E.; Fisher, S. E.; Laval, S. H.; Rue, J. E.; Stein, J. F.; Monaco, A. P. :
Confirmatory evidence for linkage of relative hand skill to 2p12-q11. (Letter) Am. J. Hum.
Genet. 72: 499-502, 2003.
PubMed ID : 12596796
10. Francks, C.; Fisher, S. E.; MacPhie, I. L.; Richardson, A. J.; Marlow, A. J.; Stein, J. F.; Monaco, A.
P. :
A genomewide linkage screen for relative hand skill in sibling pairs. Am. J. Hum. Genet. 70:
800-805, 2002. Note: Erratum: Am. J. Med. Genet. 70: 1074 only, 2002.
PubMed ID : 11774074
11. Geschwind, D. H.; Miller, B. L.; DeCarli, C.; Carmelli, D. :
Heritability of lobar brain volumes in twins supports genetic models of cerebral laterality
and handedness. Proc. Nat. Acad. Sci. 99: 3176-3181, 2002.
PubMed ID : 11867730
12. Geschwind, N.; Behan, P. :
Left-handedness: association with immune disease, migraine, and developmental learning
disorder. Proc. Nat. Acad. Sci. 79: 5097-5100, 1982.
PubMed ID : 6956919
13. Halpern, D. F.; Coren, S. :
Do right-handers live longer? (Letter) Nature 333: 213, 1988.
PubMed ID : 3367996
14. Halpern, D. F.; Coren, S. :
Handedness and life span. (Letter) New Eng. J. Med. 324: 998, 1991.
PubMed ID : 2002827
15. Hicks, R. E.; Kinsbourne, M. :
Human handedness: a partial cross-fostering study. Science 192: 908-910, 1976.
PubMed ID : 1273577
16. Huheey, J. E. :
Concerning the origin of handedness in humans. Behav. Genet. 7: 29-32, 1977.
PubMed ID : 843315
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17. Klar, A. J. S. :
A single locus, RGHT, specifies preference for hand utilization in humans. Cold Spring
Harbor Symp. Quant. Biol. 61: 59-65, 1996.
PubMed ID : 9246435
18. Laland, K. N.; Kumm, J.; Van Horn, J. D.; Feldman, M. W. :
A gene-culture model of human handedness. Behav. Genet. 25: 433-445, 1995.
PubMed ID : 7487840
19. Lander, E.; Kruglyak, L. :
Genetic dissection of complex traits: guidelines for interpreting and reporting linkage
results. Nature Genet. 11: 241-247, 1995.
PubMed ID : 7581446
20. Levy, J. :
A review of evidence for a genetic component in the determination of handedness. Behav.
Genet. 6: 429-453, 1976.
PubMed ID : 791243
21. Levy, J.; Nagylaki, T. :
A model for the genetics of handedness. Genetics 72: 117-128, 1972.
PubMed ID : 5073852
22. Olsson, H.; Ingvar, C. :
Left handedness is uncommon in breast cancer patients. Europ. J. Cancer 27: 1694-1695,
1991.
23. Rife, D. C. :
Handedness with special reference to twins. Genetics 25: 178-186, 1940.
24. Schur, P. H. :
Handedness in systemic lupus erythematosus. Arthritis Rheum. 29: 419-420, 1986.
PubMed ID : 3964317
25. Springer, S. P.; Searleman, A. :
Laterality in twins: the relationship between handedness and hemispheric asymmetry for
speech. Behav. Genet. 8: 349-357, 1978.
PubMed ID : 567977
26. Williamson, R. :
Personal Communication. London, England, 6/1/1986.
CONTRIBUTORS
Victor A. McKusick - updated : 2/27/2003
Victor A. McKusick - updated : 4/16/2002
Victor A. McKusick - updated : 3/22/2002
Victor A. McKusick - updated : 1/14/2002
Victor A. McKusick - updated : 9/3/1997
Orest Hurko - updated : 1/25/1996
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OMIM - *139900 HAND SKILL, RELATIVE; HSR
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CREATION DATE
Victor A. McKusick : 6/4/1986
EDIT HISTORY
carol : 7/10/2003
tkritzer : 3/3/2003
terry : 2/27/2003
cwells : 5/1/2002
cwells : 4/24/2002
terry : 4/16/2002
alopez : 4/2/2002
cwells : 3/28/2002
terry : 3/22/2002
carol : 1/15/2002
mcapotos : 1/15/2002
terry : 1/14/2002
terry : 6/3/1998
jenny : 9/9/1997
terry : 9/3/1997
terry : 9/3/1997
terry : 7/7/1997
terry : 4/15/1996
mark : 1/25/1996
terry : 1/22/1996
carol : 1/27/1995
mimadm : 9/24/1994
davew : 8/5/1994
terry : 7/18/1994
carol : 4/14/1992
supermim : 3/16/1992
Copyright © 1966-2004 Johns Hopkins University
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