title: Inheritance of the 8.1 ancestral haplotype in recurrent pregnancy loss.
abstract: OBJECTIVE
  The 8.1 ancestral haplotype (AH) (HLA-A1, C7, B8, C4AQ0, C4B1, DR3, DQ2) is a remarkably long and conserved haplotype in the human major histocompatibility complex. It has been associated with both beneficial and detrimental effects, consistent with antagonistic pleiotropy. It has also been proposed that the survival of long, conserved haplotypes may be due to gestational drive, i.e. selective miscarriage of fetuses who have not inherited the haplotype from a heterozygous mother. Recurrent pregnancy loss (RPL) is defined as three or more consecutive pregnancy losses. The objective was to test the gestational drive theory for the 8.1AH in women with RPL and their live born children.
  
  
  METHODS
  We investigated the inheritance of the 8.1AH from 82 heterozygous RPL women to 110 live born children. All participants were genotyped for HLA-A, -B and -DRB1 in DNA from EDTA-treated blood or buccal swaps. Inheritance was compared with a Mendelian inheritance of 50% using a two-sided exact binomial test.
  
  
  RESULTS
  We found that 55% of the live born children had inherited the 8.1AH, which was not significantly higher than the expected 50% (P = 0.29). Interestingly, we found a non-significant trend toward a higher inheritance of the 8.1AH in girls, 63%, P = 0.11 as opposed to boys, 50%, P = 1.00.
  
  
  CONCLUSIONS
  We did not find that the 8.1AH was significantly more often inherited by live born children of 8.1AH heterozygous RPL women. However our data suggest that there may be a sex-specific effect which would be interesting to explore further, both in RPL and in a background population.
authors.affiliation: Recurrent Pregnancy Loss Unit, Fertility Clinic 4071, University Hospital Copenhagen Rigshospitalet, Blegdamsvej 9, Copenhagen Ø 2100, Denmark; astrid.marie.kolte@regionh.dk.
authors.forename: Astrid M
authors.initials: AM
authors.lastname: Kolte
authors.affiliation: Recurrent Pregnancy Loss Unit, Fertility Clinic 4071, University Hospital Copenhagen Rigshospitalet, Blegdamsvej 9, Copenhagen Ø 2100, Denmark;
authors.forename: Henriette S
authors.initials: HS
authors.lastname: Nielsen
authors.affiliation: Department of Clinical Immunology, Aalborg University Hospital, North, Urbansgade 32, Aalborg 9000, Denmark;
authors.forename: Rudi
authors.initials: R
authors.lastname: Steffensen
authors.affiliation: Human Evolutionary Studies Program and Department of Biological Sciences, Simon Fraser University, 8888 University Drive, Burnaby, BC V5A 1S6, Canada and.
authors.forename: Bernard
authors.initials: B
authors.lastname: Crespi
authors.affiliation: Recurrent Pregnancy Loss Unit, Fertility Clinic 4071, University Hospital Copenhagen Rigshospitalet, Blegdamsvej 9, Copenhagen Ø 2100, Denmark; Department of Gynecology and Obstetrics, Aalborg University Hospital North, Reberbansgade 15, Aalborg 9000, Denmark.
authors.forename: Ole B
authors.initials: OB
authors.lastname: Christiansen
keywords: cohort study; gestational drive; mother–offspring conflict; recurrent pregnancy loss; selfish gene theory