CONTEXT: The variability of human fetal growth is multifactorial. Twin and family studies demonstrate that genetic determinants influence normal fetal growth, but the responsible genetic polymorphisms are unknown. OBJECTIVE: The objective of the study was the mapping of quantitative trait loci (QTLs) for birth length and weight. DESIGN AND METHODS: To approach the genetic factors implicated in the normal variation of birth length and weight, we conducted a genome-wide approach of these two quantitative traits in 220 French Caucasian pedigrees (412 sibling pairs) using a variance components method. RESULTS: We observed evidence for several QTLs influencing birth length or birth weight independently. Whereas birth length and weight showed a close correlation (r = 0.76, P < 0.0001), their genetic variability appeared largely determined by distinct genomic loci. Birth length was influenced by two major QTLs located in 2p21 and 2q11 (LOD scores 2.69 and 3.57). The variability of birth weight was linked to another QTL on 7q35 (LOD score 3.1). Several other regions showed more modest evidence for linkage with LOD score values of 1-2 on chromosomes 7, 8, 10, 13, and 17 for birth length and chromosomes 1, 2, 6, 8, 10, 13, 14, 15, 17, and 20 for birth weight. CONCLUSION: These preliminary QTLs provide a first step toward the identification of the genomic variants involved in the variability of human fetal growth. Our results should, however, be considered preliminary until they are replicated in other studies.
CONTEXT: The variability of human fetal growth is multifactorial. Twin and family studies demonstrate that genetic determinants influence normal fetal growth, but the responsible genetic polymorphisms are unknown. OBJECTIVE: The objective of the study was the mapping of quantitative trait loci (QTLs) for birth length and weight. DESIGN AND METHODS: To approach the genetic factors implicated in the normal variation of birth length and weight, we conducted a genome-wide approach of these two quantitative traits in 220 French Caucasian pedigrees (412 sibling pairs) using a variance components method. RESULTS: We observed evidence for several QTLs influencing birth length or birth weight independently. Whereas birth length and weight showed a close correlation (r = 0.76, P < 0.0001), their genetic variability appeared largely determined by distinct genomic loci. Birth length was influenced by two major QTLs located in 2p21 and 2q11 (LOD scores 2.69 and 3.57). The variability of birth weight was linked to another QTL on 7q35 (LOD score 3.1). Several other regions showed more modest evidence for linkage with LOD score values of 1-2 on chromosomes 7, 8, 10, 13, and 17 for birth length and chromosomes 1, 2, 6, 8, 10, 13, 14, 15, 17, and 20 for birth weight. CONCLUSION: These preliminary QTLs provide a first step toward the identification of the genomic variants involved in the variability of human fetal growth. Our results should, however, be considered preliminary until they are replicated in other studies.
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