TY - JOUR
T1 - Ionizing radiation and genetic risks. V. Multifactorial diseases
T2 - A review of epidemiological and genetic aspects of congenital abnormalities in man and of models on maintenance of quantitative traits in populations
AU - Sankaranarayanan, K.
AU - Yasuda, N.
AU - Chakraborty, R.
AU - Tusnady, G.
AU - Czeizel, A. E.
N1 - Funding Information:
This work was supportebdy EuratomC ontract FI3P-CT92-005a nd by Atomic Energy Control Board of Canada( AECB Project No. 7.167.1)t o one of us (K.S). We are grateful to Dr. R.R. Frants,D epartmenotf Human GeneticsU, niver-sity of Leiden and the three refereesf or their valuablec ommentsa nd Dr. V. Elaguppilai,A - tomic Energy Control Board of Canadaf or providing accesst o the ResearchR eportof Anderson and colleagues( INFO-0255) submittedt o AECB.
PY - 1994/2
Y1 - 1994/2
N2 - This paper discusses (a) data on the epidemiological and etiological aspects of human congenital abnormalities, (b) the multifactorial threshold model and other models which have been proposed to explain their inheritance patterns and recurrence risks in families and (c) current concepts on mechanisms on the prevalence of heritable variation for quantitative traits in populations. Congenital abnormalities, which afflict an estimated 6% of all live births, are etiologically heterogeneous. The majority of these do not follow Mendelian transmission patterns, but do 'run' in families. The multifactorial threshold model is an extension of genetic principles developed for quantitative traits to all-or-none traits; in its simplest formulation, it assumes the existence in the population of an underlying normally distributed 'liability' (which is due to numerous genetic and environmental factors acting additively, each contributing a small amount of liability) and of a 'threshold' beyond which the individual is affected. For most congenital abnormalities, the nature of these factors remains unknown. Other models assume fewer causal factors although, again, these remain to be identified. The question of how considerable heritable variation for most quantitative / polygenic traits has come to exist is a long-standing one in evolutionary population genetics. Models postulating that its existence is consistent with a balance between recurrent mutation and stabilizing selection or suggesting the possible operation of other mechanisms have been published in the literature.
AB - This paper discusses (a) data on the epidemiological and etiological aspects of human congenital abnormalities, (b) the multifactorial threshold model and other models which have been proposed to explain their inheritance patterns and recurrence risks in families and (c) current concepts on mechanisms on the prevalence of heritable variation for quantitative traits in populations. Congenital abnormalities, which afflict an estimated 6% of all live births, are etiologically heterogeneous. The majority of these do not follow Mendelian transmission patterns, but do 'run' in families. The multifactorial threshold model is an extension of genetic principles developed for quantitative traits to all-or-none traits; in its simplest formulation, it assumes the existence in the population of an underlying normally distributed 'liability' (which is due to numerous genetic and environmental factors acting additively, each contributing a small amount of liability) and of a 'threshold' beyond which the individual is affected. For most congenital abnormalities, the nature of these factors remains unknown. Other models assume fewer causal factors although, again, these remain to be identified. The question of how considerable heritable variation for most quantitative / polygenic traits has come to exist is a long-standing one in evolutionary population genetics. Models postulating that its existence is consistent with a balance between recurrent mutation and stabilizing selection or suggesting the possible operation of other mechanisms have been published in the literature.
KW - Genetic risk
KW - Ionizing radiation
KW - Multifactorial diseases
UR - http://www.scopus.com/inward/record.url?scp=13844323749&partnerID=8YFLogxK
U2 - 10.1016/0165-1110(94)90009-4
DO - 10.1016/0165-1110(94)90009-4
M3 - Review article
C2 - 7507570
AN - SCOPUS:13844323749
SN - 0165-1110
VL - 317
SP - 1
EP - 23
JO - Mutation Research/Reviews in Genetic Toxicology
JF - Mutation Research/Reviews in Genetic Toxicology
IS - 1
ER -