Biomedical subjects

Susan L Christian

Publications and source records attributed to Susan L Christian.

5 recordsLinked to original sources

PubMed2004

Autism as a paradigmatic complex genetic disorder.

Autism is one of the most heritable complex disorders, with compelling evidence for genetic factors and little or no support for environmental influence. The estimated prevalence of autism has increased since molecular genetic studies began, owing to loosening of diagnostic criteria and, more importantly, to more complete ascertainment strategies. This has led to a reduction in the sibling relative risk, but strong heritability estimates remain. It is essential to recognize that genetics is the only current approach to understanding the pathophysiology of autism in which there is not the usual concern about whether one is studying a consequence rather than a cause. There are hundreds, if not thousands, of patients with autism spectrum disorder with documented single-gene mutations or chromosomal abnormalities. Autism may be one of the most complex, yet strongly genetic, disorders in which chromosomal disorders, relatively rare highly penetrant mutations, and multiplicative effects of common variants all have support in different cases and families. The field of complex genetics is replete with many researchers and reviewers who want to promote their overly focused interest in one method at the exclusion of others. However, it is essential that the restricted interests of patients with autism not be reflected in overly restrictive genetic approaches if we are to better understand the genetics of autism in the most expeditious and thorough manner.

Alleles↗

PubMed2004

Linkage disequilibrium of the brain-derived neurotrophic factor Val66Met polymorphism in children with a prepubertal and early adolescent bipolar disorder phenotype.

OBJECTIVE: Transmission of the brain-derived neurotrophic factor (BDNF) Val66 allele in children with a prepubertal and early adolescent bipolar disorder phenotype was examined. METHOD: The prepubertal and early adolescent bipolar disorder phenotype was defined as current DSM-IV bipolar I disorder (manic or mixed phase) with at least one cardinal mania criterion (i.e., euphoria and/or grandiosity) to ensure differentiation from attention deficit hyperactivity disorder. Probands (mean age=10.7 years, SD=2.7) were obtained by consecutive new case ascertainment from designated pediatric and psychiatric venues. Parents and probands were interviewed separately by research nurses who were blind to the probands' diagnoses. Genotyping was done with TaqMan Assay-on-Demand. Analysis was done with the Family Based Association Test program. RESULTS: There were 53 complete, independent trios. The BDNF Val66 allele was preferentially transmitted (Family Based Association Test: chi(2)=6.0, df=1, p=0.014). CONCLUSIONS: This finding in child bipolar disorder is consistent with data for adults with bipolar disorder that show preferential transmission of the Val66 allele.

Adolescent↗

PubMed2003

DNannotator: Annotation software tool kit for regional genomic sequences.

Sequence annotation is essential for genomics-based research. Investigators of a specific genomic region who have developed abundant local discoveries such as genes and genetic markers, or have collected annotations from multiple resources, can be overwhelmed by the difficulty in creating local annotation and the complexity of integrating all the annotations. Presenting such integrated data in a form suitable for data mining and high-throughput experimental design is even more daunting. DNannotator, a web application, was designed to perform batch annotation on a sizeable genomic region. It takes annotation source data, such as SNPs, genes, primers, and so on, prepared by the end-user and/or a specified target of genomic DNA, and performs de novo annotation. DNannotator can also robustly migrate existing annotations in GenBank format from one sequence to another. Annotation results are provided in GenBank format and in tab-delimited text, which can be imported and managed in a database or spreadsheet and combined with existing annotation as desired. Graphic viewers, such as Genome Browser or Artemis, can display the annotation results. Reference data (reports on the process) facilitating the user's evaluation of annotation quality are optionally provided. DNannotator can be accessed at http://sky.bsd.uchicago.edu/DNannotator.htm.

Chromosomes, Human, Pair 13↗

PubMed2003

Polymorphisms at the G72/G30 gene locus, on 13q33, are associated with bipolar disorder in two independent pedigree series.

Linkage evidence suggests that chromosome 13 (13q32-33) contains susceptibility genes for both bipolar disorder and schizophrenia. Recently, genes called "G72" and "G30" were identified, and polymorphisms of these overlapping genes were reported to be associated with schizophrenia. We studied two series of pedigrees with bipolar disorder: the Clinical Neurogenetics (CNG) pedigrees (in which linkage to illness had been previously reported at 13q32-33), with 83 samples from 22 multiplex families, and the National Institute of Mental Health (NIMH) Genetics Initiative pedigrees, with 474 samples from 152 families. Sixteen single-nucleotide polymorphisms (SNPs) were genotyped at and around the G72/G30 locus, which covered a 157-kb region encompassing the entire complementary DNA sequences of G72 and G30. We performed transmission/disequilibrium testing (TDT) and haplotype analysis, since a linkage-disequilibrium block was present at this gene locus. In the CNG and NIMH data sets, the results of global TDT of the entire haplotype set were significant and consistent (P=.0004 and P=.008, respectively). In the CNG series, the associated genotypes divided the families into those with linkage and those without linkage (partitioned by the linkage evidence). Analysis of the decay of haplotype sharing gave a location estimate that included G72/G30 in its 95% confidence interval. Although statistically significant association was not detected for individual SNPs in the NIMH data set, the same haplotype was consistently overtransmitted in both series. These data suggest that a susceptibility variant for bipolar illness exists in the vicinity of the G72/G30 genes. Taken together with the earlier report, this is the first demonstration of a novel gene(s), discovered through a positional approach, independently associated with both bipolar illness and schizophrenia.

Alternative Splicing↗

PubMed2002

An evaluation of the assembly of an approximately 15-Mb region on human chromosome 13q32-q33 linked to bipolar disorder and schizophrenia.

The human 13q32-q33 region has been linked to both bipolar disorder and schizophrenia. Before completion of the draft sequences, we developed an approximately 15-Mb comprehensive map for the region extending from D13S1300 to ATA35H12. This map was assembled using publicly available mapping data and sequence-tagged site (STS)-based PCR confirmation. We then compared this map with the NCBI, Celera Genomics, and UCSC Golden Path data in February, June, and September 2001. All data sets showed gaps, misassignment of STSs, and errors in orientation and marker order. Surprisingly, the completed sequences of many bacterial artificial chromosomes (BACs) had been truncated. Of 21 gaps that were detected, 4 were present in both the NCBI and Celera databases. All gaps could be filled using 1-2 BAC clones. A total of 39 loci mapped to additional sites within the human genome, providing evidence of segmental duplications. Additionally, 61 unique cDNA clones were sequenced to increase available transcribed sequence, and 11,353 reference single-nucleotide polymorphisms (SNPs) with an average density of 1 SNP/3720 bases were identified. Overall, integration of the data from multiple sources is still needed for complete assembly of the 13q32-q33 region. (c)

Bipolar Disorder↗