TY - JOUR
T1 - Effects of isolation and inbreeding on human quantitative traits
T2 - an example of biochemical markers of hemostasis and inflammation
AU - Pulanić, Drazen
AU - Polasek, Ozren
AU - Petrovecki, Mladen
AU - Vorko-Jović, Ariana
AU - Pericić, Marijana
AU - Lauc, Lovorka Barać
AU - Klarić, Irena Martinović
AU - Biloglav, Zrinka
AU - Kolcić, Ivana
AU - Zgaga, Lina
AU - Carothers, Andrew D
AU - Ramić, Senad
AU - Setić, Mia
AU - Janićijević, Branka
AU - Narancić, Nina Smolej
AU - Bućan, Kajo
AU - Rudan, Diana
AU - Lowe, Gordon
AU - Rumley, Ann
AU - Rudan, Pavao
AU - Campbell, Harry
AU - Rudan, Igor
PY - 2008
Y1 - 2008
N2 - Isolation is a known force in evolutionary biology and one of the main factors in speciation. One of the main consequences of severe isolation is reduced mate choice, which results in the occurrence of inbreeding as a result of isolation. We investigated the effects of individual genome-wide heterozygosity measured as the multilocus heterozygosity (MLH) on biochemical markers of hemostasis and inflammation in 1,041 individuals from the island of Vis, Croatia, where inbreeding is prevalent and a wide range of variation in the genome-wide heterozygosity is expected. Assessment of individual genome-wide heterozygosity was based on genome-wide scans using 800 microsatellite (STR) and 317,503 single nucleotide (SNP) polymorphic markers in each examinee. In addition, for each examinee we defined a personal genetic history (PGH) based on genealogical records. The association between PGH and MLH and fibrinogen, D-dimer (Dd), von Willebrand factor (vWF), tissue plasminogen activator (tPA), and C-reactive protein (CRP) was performed with a mixed model, controlling for possible confounding effects. PGH was a significant predictor only for tPA (P <0.001), whereas neither of the two MLH measures exhibited significant association with any of the investigated traits. The effects of individual genome-wide heterozygosity are most likely expressed in highly polygenically determined traits or in traits that are mediated by rare and recessive genetic variants. Weak associations between PGH and MLH and markers of hemostasis and inflammation suggest that their genetic control may not be highly polygenic and that they could be promising targets for genetic association studies.
AB - Isolation is a known force in evolutionary biology and one of the main factors in speciation. One of the main consequences of severe isolation is reduced mate choice, which results in the occurrence of inbreeding as a result of isolation. We investigated the effects of individual genome-wide heterozygosity measured as the multilocus heterozygosity (MLH) on biochemical markers of hemostasis and inflammation in 1,041 individuals from the island of Vis, Croatia, where inbreeding is prevalent and a wide range of variation in the genome-wide heterozygosity is expected. Assessment of individual genome-wide heterozygosity was based on genome-wide scans using 800 microsatellite (STR) and 317,503 single nucleotide (SNP) polymorphic markers in each examinee. In addition, for each examinee we defined a personal genetic history (PGH) based on genealogical records. The association between PGH and MLH and fibrinogen, D-dimer (Dd), von Willebrand factor (vWF), tissue plasminogen activator (tPA), and C-reactive protein (CRP) was performed with a mixed model, controlling for possible confounding effects. PGH was a significant predictor only for tPA (P <0.001), whereas neither of the two MLH measures exhibited significant association with any of the investigated traits. The effects of individual genome-wide heterozygosity are most likely expressed in highly polygenically determined traits or in traits that are mediated by rare and recessive genetic variants. Weak associations between PGH and MLH and markers of hemostasis and inflammation suggest that their genetic control may not be highly polygenic and that they could be promising targets for genetic association studies.
U2 - 10.3378/1534-6617-80.5.513
DO - 10.3378/1534-6617-80.5.513
M3 - Article
C2 - 19341321
SN - 0018-7143
VL - 80
SP - 513
EP - 533
JO - Human Biology: The Official Publication of the American Association of Anthropological Genetics
JF - Human Biology: The Official Publication of the American Association of Anthropological Genetics
IS - 5
ER -