Assessment & Research

Exclusion of linkage to the HLA region in ninety multiplex sibships with autism.

Rogers et al. (1999) · Journal of autism and developmental disorders 1999
★ The Verdict

The HLA region on chromosome 6 shows no excess sharing in multiplex autism families, so it is probably not a major autism gene.

✓ Read this if BCBAs who field parent questions about genetic testing or heritability.
✗ Skip if Clinicians only focused on behavior intervention, not genetics talk.

01Research in Context

01

What this study did

Scientists looked at ninety families. Each family had more than one child with autism.

They checked if brothers and sisters shared the same HLA genes on chromosome 6. Shared genes would mean the spot is linked to autism.

02

What they found

The kids did not share HLA alleles more than chance. The region showed no link to autism.

This tells us the HLA area is probably not a big autism gene hot spot.

03

How this fits with other research

Allen-Brady et al. (2010) later found a hint of linkage on the X chromosome in high-risk families. They used the same kind of multiplex families but looked elsewhere after this null result.

Castermans et al. (2004) wrote a review saying linkage scans often come up empty. They urged the field to hunt chromosome breaks instead of doing more big scans.

Gaily et al. (1998) had earlier looked for big chromosome changes in kids with PDDs and found very few. Together these papers show the move from eyeballing chromosomes under the microscope to DNA-level linkage hunts.

04

Why it matters

When you talk genes with families, you can say the HLA region is unlikely to cause autism. Focus risk counseling on newer findings or on broad heritability, not on this old candidate spot.

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→ Action — try this Monday

Drop any mention of HLA 'autism risk genes' in parent handouts; update to say 'many genes, each with small effect.'

02At a glance

Intervention
not applicable
Design
other
Sample size
97
Population
autism spectrum disorder
Finding
null

03Original abstract

Several studies have suggested a role for the histocompatibility complex of loci (HLA) in the genetic susceptibility to autism. We have tested this hypothesis by linkage analysis using genetic marker loci in the HLA region on chromosome 6p in multiplex families with autism. We have examined sharing of alleles identical by descent in 97 affected sib pairs from 90 families. Results demonstrate no deviation from the null expectation of 50% sharing of alleles in this region; in fact, for most marker loci, the observed sharing was less than 50%. Thus, it is unlikely that loci in this region contribute to the genetic etiology of autism to any significant extent in our families.

Journal of autism and developmental disorders, 1999 · doi:10.1023/a:1023075904742