Autism Speaks, Science, Latest Research, AGRE, 2004

<< Return to the AGRE main page

2005 | 2004 | 2003 | 2002 | 2001

Talebizadeh Z, Bittel DC, Veatch OJ, Butler MG, Takahashi TN, Miles JH.
Do known mutations in neuroligin genes (NLGN3 and NLGN4) cause autism?
PMID: 15679194
J Autism Dev Disord. 2004 Dec;34(6):735-6.
Summary by AGRE's Researcher Liaison Vlad Kustanovich Ph.D.:

A group of scientists, known as the PARIS group, have identified a genetic association between autism and two neuroligin genes. Since then, several other groups have tried to understand the involvement of these genes in autism.
There are compelling reasons why these are attractive candidate genes. Neuroligin proteins play critical roles in the process of creating and maintaining connections in the brain, a process known as synaptogenesis.
Further research has shown these genes are found on the X chromosome, which would explain why there is such a remarkable male bias in affected children.
To determine whether these genes are generally involved - or were specific to the families in the previous studies - Dr. Talebizadeh and colleagues tested for the presence of the mutations within the AGRE families, as well as from the University of Missouri-Columbia Hospital.
The mutations previously identified were not present in the study population. While the sample size in this study was fairly small (67 families), it indicates that the mutations identified by the PARIS group do not appear to be generally involved in the autistic United States populations.

Rabionet R, Jaworski JM, Ashley-Koch AE, Martin ER, Sutcliffe JS, Haines JL, Delong GR, Abramson RK, Wright HH, Cuccaro ML, Gilbert JR, Pericak-Vance MA.
Analysis of the autism chromosome 2 linkage region: GAD1 and other candidate genes.
PMID:15542242
Neurosci Lett. 2004 Dec 6;372(3):209-14.
Summary by AGRE's Researcher Liaison Vlad Kustanovich Ph.D.:

There has been a flurry of research into chromosome 2q after several reports indicated a genetic link to autism at the chromosome 2q region. Two additional reports identified a subset of families that showed a more striking level of linkage in this area. The autistic children in these families were notable because they had a more pronounced difficulty speaking in phrases rather than single words.
There are a large number of genes that appear to be promising candidates for influencing autism susceptibility. A group of scientists at Duke University, the W.S. Hall Psychiatric Institute and Vanderbilt University, sought to replicate these linkage findings.
While the findings were not overwhelming, there was evidence linked to the 2q region. To bolster their findings, the researchers added 99 AGRE families to their data sets and examined specific candidate genes in the 2q region.
The researchers selected genetic changes (variants) in nine genes in this region that appeared to be candidates. Some genes, such as GAD1 and HOXD1, are involved in the functioning and development of the nervous system. Others, such as CD28 and CTLA4, play a role in the operation of the immune system.
A study was conducted with each gene, as well as its genetic variants, to determine if there is a connection between the transmission of the genetic changes from parent to affected child.
Of the families tested, only three genes showed mild association with autism. Two of the three genes (DLX6 and HOXD1) are involved in the development of the nervous system. The third gene, ABI2, is also believed to play a role in synaptic pruning, whereby the excess nerve cells are removed from the brain.
Despite these modest associations, researchers admitted it is not likely that any of these genes play major roles in autism susceptibility. However, they may still be involved as modifiers of major genes that contribute to autism susceptibility.

Skaar DA, Shao Y, Haines JL, Stenger JE, Jaworski J, Martin ER, Delong GR, Moore JH, McCauley JL, Sutcliffe JS, Ashley-Koch AE, Cuccaro ML, Folstein SE, Gilbert JR, Pericak-Vance MA.
Analysis of the RELN gene as a genetic risk factor for autism.
PMID:15558079
Mol Psychiatry. 2004 Nov 23
Summary by AGRE's Researcher Liaison Vlad Kustanovich Ph.D.:

Several genome-wide scans of autism identified a region on the long arm of chromosome 7 as a likely site where an autism susceptibility gene may reside. Among the most promising candidate genes in this region is the gene RELN (pronounced reelin).
RELN encodes a protein that is crucial to the formation of connections among brain cells. This protein also plays a role in the early development of the brain by controlling where and how the brain cells orient themselves.
To further explore the potential association of RELN with autism, scientists at Duke University, Vanderbilt University and Tufts, collaborated by pooling their families with those from the AGRE collection.
These researchers examined the transmission rates of specific genetic variants from parents to affected children. The variants serve as a way to monitor the transmission of gene forms at particular points in the DNA. Five variants in the RELN were tested, as well as a few in two genes that are situated on either side of RELN. Two genetic markers in RELN were shown to be associated with autism. None of the genetic markers in the surrounding genes showed any evidence of association.
The scientists then examined the contribution of each family set to the association between RELN and autism. Interestingly, they found that the AGRE families disproportionately contributed the most significant association, while Duke and Tufts families contributed to a lesser extent.
This demonstrates the variability that can occur between studies when an association is found and then refuted. There are many reasons for this variability. One is the potential difference in the underlying causes of autism on a systemic level. Another possibility is mutations at the DNA level.
For this reason, geneticists attempt to study as many families with autism as possible to validate their results. With a greater number of family samples, geneticists can study families with autism in groups based on potential biological factors, without eroding the statistical significance of their findings.

Junaid MA, Kowal D, Barua M, Pullarkat PS, Sklower Brooks S, Pullarkat RK.
Proteomic studies identified a single nucleotide polymorphism in glyoxalase I as autism susceptibility factor.
PMID:15386471
Am J Med Genet. 2004 Nov 15;131A(1):11-7.

Stone JL, Merriman B, Cantor RM, Yonan AL, Gilliam TC, Geschwind DH, Nelson SF.
Evidence for Sex-Specific Risk Alleles in Autism Spectrum Disorder.
PMID:15467983
Am J Hum Genet. 2004 Oct 5;75(6)

McCauley JL, Olson LM, Delahanty R, Amin T, Nurmi EL, Organ EL, Jacobs MM, Folstein SE, Haines JL, Sutcliffe JS.
A linkage disequilibrium map of the 1-Mb 15q12 GABA(A) receptor subunit cluster and association to autism.
PMID:15389768
Am J Med Genet. 2004 Aug 24

Jiang YH, Sahoo T, Michaelis RC, Bercovich D, Bressler J, Kashork CD, Liu Q, Shaffer LG, Schroer RJ, Stockton DW, Spielman RS, Stevenson RE, Beaudet AL.
A mixed epigenetic/genetic model for oligogenic inheritance of autism with a limited role for UBE3A.
PMID:15389703
Am J Med Genet. 2004 Aug 30

Vincent JB, Kolozsvari D, Roberts WS, Bolton PF, Gurling HM, Scherer SW.
Mutation screening of X-chromosomal neuroligin genes: no mutations in 196 autism probands.
PMID:15274046
Am J Med Genet. 2004 Aug 15;129B(1):82-4.

Kolevzon A, Smith CJ, Schmeidler J, Buxbaum JD, Silverman JM.
Familial symptom domains in monozygotic siblings with autism.
PMID:15274045
Am J Med Genet. 2004 Aug 15;129B(1):76-81.

Persico AM, D'Agruma L, Zelante L, Militerni R, Bravaccio C, Schneider C, Melmed R, Trillo S, Montecchi F, Elia M, Palermo M, Rabinowitz D, Pascucci T, Puglisi-Allegra S, Reichelt KL, Muscarella L, Guarnieri V, Melgari JM, Conciatori M, Keller F.
Enhanced APOE2 transmission rates in families with autistic probands.
PMID:15167692
Psychiatr Genet. 2004 Jun;14(2):73-82.

Serajee FJ, Nabi R, Zhong H, Huq M.
Polymorphisms in xenobiotic metabolism genes and autism.
PMID:15446388
J Child Neurol. 2004 Jun;19(6):413-7.

McCauley JL, Olson LM, Dowd M, Amin T, Steele A, Blakely RD, Folstein SE, Haines JL, Sutcliffe JS.
Linkage and association analysis at the serotonin transporter (SLC6A4) locus in a rigid-compulsive subset of autism.
PMID:15108191
Am J Med Genet. 2004 May 15;127B(1):104-12.

Ramoz N, Reichert JG, Smith CJ, Silverman JM, Bespalova IN, Davis KL, Buxbaum JD.
Linkage and Association of the Mitochondrial Aspartate/Glutamate Carrier SLC25A12 Gene With Autism.
PMID:15056512
Am J Psychiatry. 2004 Apr;161(4):662-9.

Gharani N, Benayed R, Mancuso V, Brzustowicz LM, Millonig JH.
Association of the homeobox transcription factor, ENGRAILED 2, 3, with autism spectrum disorder.
PMID:15024396
Mol Psychiatry. 2004 Mar 16 :1-11

Conciatori M, Stodgell CJ, Hyman SL, O'Bara M, Militerni R, Bravaccio C, Trillo S, Montecchi F, Schneider C, Melmed R, Elia M, Crawford L, Spence SJ, Muscarella L, Guarnieri V, D'Agruma L, Quattrone A, Zelante L, Rabinowitz D, Pascucci T, Puglisi-Allegra S, Reichelt KL, Rodier PM, Persico AM.
Association between the HOXA1 A218G polymorphism and increased head circumference in patients with autism.
PMID:14960295
Biol Psychiatry. 2004 Feb 15;55(4):413-9.

Nabi R, Serajee FJ, Chugani DC, Zhong H, Huq AH.
Association of tryptophan 2,3 dioxygenase gene polymorphism with autism.
PMID:14755447
Am J Med Genet. 2004 Feb 15;125B(1):63-8.

Raiford KL, Shao Y, Allen IC, Martin ER, Menold MM, Wright HH, Abramson RK, Worley G, DeLong GR, Vance JM, Cuccaro ML, Gilbert JR, Pericak-Vance MA.
No association between the APOE gene and autism.
PMID:14755445
Am J Med Genet. 2004 Feb 15;125B(1):57-60.

Vincent JB, Thevarkunnel S, Kolozsvari D, Paterson AD, Roberts W, Scherer SW.
Association and transmission analysis of the FMR1 IVS10 + 14C-T variant in autism.
PMID:14755444
Am J Med Genet. 2004 Feb 15;125B(1):54-6.

Buxbaum JD, Silverman J, Keddache M, Smith CJ, Hollander E, Ramoz N, Reichert JG.
Linkage analysis for autism in a subset families with obsessive-compulsive behaviors: Evidence for an autism susceptibility gene on chromosome 1 and further support for susceptibility genes on chromosome 6 and 19.
PMID:14699429
Mol Psychiatry. 2004 Feb;9(2):144-150.