Search

Atopic dermatitis is a common skin disease frequently associated with allergic disorders such as allergic rhinitis and asthma. Controversial linkage findings between atopy and markers at chromosome 11q13 led us to search chromosome 11 for genes conferring susceptibility to atopic dermatitis and atopy. Twelve families were investigated using highly polymorphic markers and a powerful model-free linkage test. Two markers gave evidence for linkage, D11S903 (P = 0.02) and FCER1B (P = 0.005). A two-point lod-score analysis between these two markers revealed significant evidence for linkage (zmax = 4.02 at (theta = 0.0). In regard to model-dependent lod-score analyses between atopic disorders and FCER1B, two-point analysis gave a lod score of z = 0.78 whereas two-locus analysis using a recessive-dominant mode of inheritance displayed a significant lod score of z = 3.55. Only 2 of 12 families showed evidence for linkage using the latter oligogenic model. In conclusion, the results of our study map the FCER1B gene in close proximity to D11S903, support the finding of Cookson et al. implicating the IgE high-affinity receptor gene (FCER1B) at 11q13, and furthermore suggest an oligogenic mode of inheritance as well as heterogeneity in the genetic susceptibility to atopy and atopic dermatitis.

Purpose: The electroencephalographic hallmark of benign childhood epilepsy with centrotemporal spikes (BECTS, or rolandic epilepsy) are characteristically shaped centrotemporal spikes and sharp waves (CTS). This EEG trait, but not BECTS itself, has been reported to follow an autosomal dominant mode of inheritance with incomplete penetrance and age dependence. CTS therefore represents a neurobiologic marker for the increased risk of developing BECTS. Benign neonatal familial convulsions (BNFC) like BECTS is an idiopathic age-dependent epilepsy with a benign course. Observations of benign neonatal seizures and BECTS in the same individual are well documented. Neonatal seizures with benign course were found in increased numbers in a series of CTS carriers. Two genetic loci, EBN1 and EBN2, have been mapped in families with BNFC, making these two loci strong candidates for the CTS trait underlying BECTS. The aim of this study was to determine whether these two epilepsy syndromes are allelic disorders., Methods: Linkage analysis was performed in 12 families with probands with BECTS and one or more relatives with CTS in the EEG with or without BECTS by using polymorphic DNA markers., Results: Assuming an autosomal mode of inheritance with penetrances of 0.9 and 0.45, respectively, both loci were consistently excluded., Conclusions: The CTS trait and EBN1 and EBN2 segregate independently. BECTS and BNFC therefore appear to be genetically distinct entities. Benign neonatal seizures may be a underrecognized symptom of the CTS trait itself.

Chromosome 11 is a region of great interest in the search for genes for bipolar disorder. Although an initial report of linkage to 11p15 was not replicated in numerous subsequent studies, the remainder of the chromosome contains a variety of interesting candidate genes and regions. These include the D2 dopamine receptor and the site of a chromosomal translocation that has been reported to be associated with bipolar disorder. As part of a systematic survey of the genome for markers linked to bipolar disorder, we have examined 13 markers on chromosome 11 in three large Icelandic families and Amish pedigree 110. No clear evidence of linkage was obtained. The highest lod score was found at D11S29 (lod = 1.63 at theta = 0.1), which is in the general region of the reported translocation breakpoints. However, this lod is not statistically significant, and its meaning is further mitigated by strongly negative lods in two nearby flanking markers. Linkage to the D2 dopamine receptor locus was strongly excluded (lod = -4.02 at theta = 0.0). In two-point analyses, linkage to bipolar disorder could be excluded to eight of the 13 markers. Multipoint analyses, similarly, failed to reveal any evidence of linkage.

Schizophrenia is a severe mental illness with a typically chronic course affecting nearly 1% of the human population. It is generally accepted that genetic factors have an important pathogenic role in a substantial portion of schizophrenia cases; however, despite decades of family studies, there is no agreed-upon mode of inheritance. The discovery of genetic aetiologic factors and resolution of the inheritance pattern(s) will undoubtably emerge from genetic linkage studies. With these objectives in mind, we undertook a linkage project, starting in 1985, in a previously well-documented kindred from north Sweden. Multipoint linkage analyses were used to screen the proximal long arm of chromosome 5 using restriction fragment length polymorphism (RFLP) markers at five loci and the distal long arm using RFLPs at two loci, one of which was the locus for the glucocorticoid receptor. We found strong evidence against linkage between schizophrenia and the seven loci. These results, together with the positive evidence for linkage of schizophrenia with markers in the proximal long arm of chromosome 5 lead us to conclude that the genetic factors underlying schizophrenia are heterogeneous.