Confirmation of the association of the C4B null allelle in autism.

The objective of this study was to examine and attempt to confirm our previous findings of an increased frequency of the C4B null allele (C4BQ0) in subjects with autism. Newly identified subjects from Utah and Oregon were studied. Families evaluated included 85 who had a child with autism and 69 control families. Of the subjects with autism studied, 42.4% carried at least one C4BQ0, compared with 14.5% of the control subjects (p = 0.00013), with a relative risk of 4.33. Over half of the C4B null alleles in the subjects with autism involved C4A duplications. A marked increase in the ancestral haplotype 44.1 that lacks a C4B gene and has 2 C4A genes was also observed. The results of this study suggest that the human leukocyte antigen class III C4BQ0 significantly increases the risk for autism.

The transmission disequilibrium test suggests that HLA-DR4 and DR13 are linked to autism spectrum disorder.

We have evaluated possible contributions of HLA-DRB1 alleles to autism spectrum disorder (ASD) in 103 families of Caucasian descent. The DR4 allele occurred more often in probands than controls (0.007), whereas the DR13,14 alleles occurred less often in probands than controls (p = 0.003). The transmission disequilibrium test (TDT) indicated that the ASD probands inherited the DR4 allele more frequently than expected (p = 0.026) from the fathers. The TDT also revealed that fewer DR13 alleles than expected were inherited from the mother by ASD probands (p = 0.006). We conclude that the TDT results suggest that DR4 and DR13 are linked to ASD. Reasons for the parental inheritance of specific alleles are poorly understood but coincide with current genetic research noting possible parent-of-origin effects in autism.

Polymorphic distribution of the ovine prion protein (PrP) gene in scrapie-infected sheep flocks in which embryo transfer was used to circumvent the transmissions of scrapie.

The genetic sequence of the ovine prion protein (PrP) gene between codons 102 and 175 with emphasis on ovine PrP gene codons 136 and 171 was determined, and the polymorphic distribution of the ovine PrP gene in the scrapie-exposed Suffolk embryo donors and offspring from these donors that were transferred to scrapie-free recipient ewes was investigated in this study. The most common genotype was AA(136)QQ(171) (70% and 63% in the donor and offspring flocks, respectively), which is considered a high risk genotype in US Suffolk sheep. Although embryos were collected from scrapie-positive donors and many embryos had the high risk genotype, no scrapie occurred in the resulting offspring. Based upon the results of this study, we conclude that vertical transmission of scrapie can be circumvented using embryo transfer procedures even when the offspring have the high risk genotype.