Genetik der Psoriasis

Psoriasis is a complex inflammatory and cutaneous disorder with complex inheritance. Currently, the most important risk factor is HLA-CW0602 (and/or a factor in strong linkage disequilibrium with it). This risk allele particularly predisposes to early manifestation (<40 years) and affects the clinical course. To date, genome-wide linkage studies have provided 11 susceptibility loci, while only a few candidate genes have been identified, which bear comparably small odd ratios. Immunological approaches, therapeutic studies with antibodies against immunologic molecules, and candidate-gene-oriented association studies could delineate more aspects of the complex etiology of psoriasis. Increasingly, pathophysiologic and genetic findings converge, giving evidence that psoriasis can be characterized by misdirected immunologic regulation processes of keratinocytes and cells of the inborn and adaptive immune system.     

Genetik der Parkinson-Krankheit

In addition to the nine well-defined monogenic forms of Parkinson’s disease, there are numerous known genetic risk and protective variants that modulate the risk of Parkinson’s disease. Among the monogenic forms, three (PARK1/PARK4, PARK8, PARK17) follow an autosomal dominant mode of inheritance, whereas six are recessively inherited (PARK2, PARK6, PARK7, PARK9, PARK14, PARK15). Six forms have clinical characteristics very similar to those of idiopathic Parkinson’s disease (PARK1/PARK4, PARK2, PARK6, PARK7, PARK8, PARK17). Among the latter forms, late-onset PARK8 with mutations in the LRRK2 gene and early-onset PARK2 caused by mutations in the Parkin gene are by far the most common. Both the monogenic and the idiopathic forms of Parkinson’s disease share common pathophysiological mechanisms involving oxidative modification, impaired protein degradation and mitochondrial dysfunction. Therefore, monogenic forms of Parkinson’s disease can serve as human model diseases for the idiopathic forms.     

Genetik der androgenetischen Alopezie

Androgenetic alopecia (AGA, male pattern baldness [MIM 109200; MIM 300710; MIM 612421]) is the commonest form of hair loss in humans, and its prevalence is highly age-dependent. Eighty per cent of European men above the age of 70 are affected by AGA, but only 30–40% of women. In many affected individuals, particularly women, AGA causes clinically significant psychological distress. Hair loss is attributable to an altered hair cycle and miniaturization of the hair follicles. The pathogenesis is androgen dependent, and genetic predisposition is an essential prerequisite of the phenotype. Several studies have identified the androgen receptor (AR)/ectodysplasin A2 receptor (EDA2R) locus on the X-chromosome as the strongest contributing factor. Genome wide association studies have identified a further locus on chromosome 20p11. The nearest scalp expressed gene to the association signal is paired box 1 (PAX1). Although there is no obvious connection between PAX1 and the androgen signalling pathway, the pathophysiological processes underlying the association signal for chromosome 20p11 have not yet been explained. At best, currently available therapies for AGA permit the arrest of hair loss. The identification of AGA associated genes and the elucidation of their function will gradually reveal the biological causes of AGA and offer hope for the development of new therapies.     

Zur Genetik der Erythrocyten-Adenosin-Desaminase

Zusammenfassung 578 unausgewählte Blutspender und 47 Familien mit 78 Kindern aus Hessen sowie 140 Neger aus Moçambique (Stamm der Macua) wurden hinsichtlich der Adenosin-Desaminase-Phänotypen (ADA) untersucht. Die gefundenen Genfrequenzen in der Bevölkerung von Hessen sind identisch mit in England ermittelten. Die Familienuntersuchungen bestätigen ohne Ausnahme die geforderte Erbregel.In den Blutproben der Neger vom Stamm der Macua (Moçambique) wurde bis auf eine Ausnahme nur der Phänotyp ADA 1 gefunden. Die Ausnahme war ein wahrscheinlich neuer seltener Phänotyp ähnlich dem Typ ADA 1, jedoch mit einem zusätzlichen anodischen Punkt.

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Genetics of red cell adenosine deaminase gene frequencies and family studies

Summary Blood samples from 578 unrelated individuals and from 47 families with 74 children living in Hessen (Germany) and 140 blood samples from negroes living in Moçambique (the tribe of Macua) were examined for erythrocyte adenosin deaminase (ADA) polymorphism. The gene frequences in the population from Hessen are identical with those of Great Britain. The family studies verify the supposed way of heredity without any exception.In the blood samples from negroes of the tribe of the Macua (Moçambique) with only one exception the phenotype ADA 1 was found. Probably the exception was a new rare phenotype similar to the type ADA 1, but with an additional anodical spot.

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Direktor: Prof. Dr. W. Speilmann

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Untersuchung der Einwohner aus Moçambique mit Unterstützung der Deutschen Forschungsgemeinschaft.     

Die Genetik der Gerste

Ohne Zusammenfassung     

Genetik der idiopathischen Epilepsien

Idiopathic epilepsies are primarily genetic in origin and represent about 40% of all epilepsies. Mutations of genes encoding ion channels play a crucial role in the pathogenesis of monogenic forms of idiopathic epilepsies. Molecular genetic approaches are still at an early stage of development for elucidating the molecular mechanisms of the epileptogenesis of common epilepsies with genetically complex predisposition. Only a comprehensive identification of the most important susceptibility genes will allow assessment of reliable individual risk profiles and development of preventive therapy strategies.     

Genetik der nichtsyndromalen Lippen-Kiefer-Gaumen-Spalten

Nonsyndromic cleft lip with or without cleft palate (CL/P) represents one of the most common birth defects. Around 50–60% of all CL/P cases are nonsyndromic and have a complex genetic background. Association and linkage studies in the past have resulted in numerous candidate genes and regions. However, researchers have been able to replicate only some of these findings in independent samples, and the current knowledge of genetic risk factors cannot yet be used in the daily clinical routine. Knowledge of the genetic and exogenous factors contributing to clefting will lead to a comprehensive understanding of the underlying pathophysiology and will make development of new prevention strategies possible.     

Genetik der Alopecia areata

Alopecia areata (AA) has a lifetime prevalence of 1–2% in both sexes and is the second most common cause of hair loss in humans. AA is a nonscarring, reversible, circumscribed hair loss with sudden onset and a recurrent course. It predominantly affects the scalp, although all hair-bearing areas of the skin may be affected. A familial occurrence of AA is well established, with recurrence risks of 5–6% in children of affected individuals. The pattern of familiality suggests that the genetic basis is multifactorial. The notion that AA may be autoimmune in nature has received strong support from association with specific HLA alleles and with the W620 variant of the PTPN22 gene (protein tyrosine phosphatase, nonreceptor type 22). Additional genetic loci have been suggested by genome-wide linkage studies in human and rodent animal models, with the responsible genes awaiting identification at the molecular level. The following review presents a summary of the latest insights into the genetics of AA and an overview of anticipated future developments.     

Genetik der Nikotinabhängigkeit

Nicotine dependence is a heritable disorder predictive of difficulty with smoking cessation and carries most of the morbidity associated with smoking. Several independent studies have shown an allelic association between nicotine dependence and DNA variants in the region of the α5-α3-β4 nicotinic receptor gene cluster on chromosome 15. Interestingly, the same region has been associated with lung cancer and chronic obstructive pulmonary disease. This highlights the importance of understanding the genetics of nicotine dependence in the context of smoking-related illness.     

Zur Genetik der gesprenkelten Haustaube

Ohne ZusammenfassungHierzu Tafel 1–3     

Genetik der nichtsyndromalen geistigen Behinderung

Most patients with mental retardation (MR) are nonsyndromic; i.e. they either have no accompanying clinical, radiological, or metabolic abnormalities, or their additional features are not specific enough to enable allocation to a recognizable malformation syndrome. Numerous novel disease genes for X-chromosomal nonsyndromic MR (NS-MR) have been elucidated in recent years, and research into autosomal forms of NS-MR has yielded first results. Both forms have turned out to be characterized by extreme genetic heterogeneity. Routine diagnostic mutation screening in the known NS-MR genes is currently not feasible in sporadic patients but will be facilitated by novel sequencing technologies in the near future. Patients with familial NS-MR should be offered inclusion in ongoing research programmes. Several X-chromosomal NS-MR genes demand consideration in the routine diagnostic workup of MR patients because they overlap phenotypically with syndromic forms of MR.     

Zur formalen Genetik der Pseudocholinesterasen

Ohne Zusammenfassung     

Zur Genetik der menschlichen Blutgruppen

Ohne ZusammenfassungAuszugsweise, auf Einladung der Deutschen Gesellschaft für Vererbungswissenschaft als einleitender Vortrag auf der Tagung 1928 (Naturforscherversammlung Hamburg) vorgetragen.Mit 26 Textfiguren