Androgen receptor (AR) gene CAG polymorphisms may be associated with body shape, and are associated with certain breast and prostate cancers. In addition, body shape is associated with risk for a variety of diseases, including heart disease, diabetes, and certain forms of cancer. The CAG repeat in exon l of the AR gene was quantified using Perkin Elmer Applied Biosystems GeneScan analysis software in 96 and 59 healthy Caucasian men and women, respectively, who were over the age of 50 years. All participants had body measurements taken and donated a blood sample. Waist measurements included circumferences at the 1) umbilicus (wstumb), 2) top of the iliac crest (wstili), and 3) midpoint between the lowest rib and the iliac crest (wstwst). Waist-hip ratio (Wl-IR) was calculated using each corresponding waist measurement, respectively (WHRUMB, WHRILI, WHRWST). Mean repeat length was significantly different (p < 0.01) between men (22 ± 0.3 repeats) and women (23 ± 0.3 repeats). There was a significant relationship (p < 0.05) between mean individual CAG repeat number and tertile of WHRUMB in women based on the mean number of CAG repeats for each woman. Waist measurements in women were significantly different for all pairwise comparisons (p < 0.05). In addition, the three measurements of WHR in women, WHRUMB, WHRILI, and WHRWST, were significantly different from each other (p < 0.05). Thus, lesser numbers of CAG repeats may indicate a more androgenic phenotype in women.

EcoP15I ist ein Vertreter der multifunktionalen, heterooligomeren Typ III Restriktionsendonukleasen. Typ III Restriktionsendonukleasen sind wegen der Lage ihres Spaltortes, ca. 25 bp vom Erkennungsort entfernt, von besonderem Interesse für Anwendungen in der Medizin und funktionellen Genomanalyse. EcoP15I erkennt die DNA-Sequenz 5''-CAGCAG und benötigt für eine effektive DNA-Spaltung zwei invers orientierte Erkennungsorte auf einem DNA-Molekül. Nach dem bisherigen DNA-Translokations-Modell bindet je ein EcoP15I-Protein an je einen Erkennungsort und startet dann durch ATP-Hydrolyse vermittelte DNA-Translokation. Die Kollision der beiden EcoP15I-DNA-Komplexe initiiert die DNA-Doppelstrang-Spaltung. Experimente zur Erkennungsort-Suche von EcoP15I zeigen, dass über längere Distanzen offenbar nicht das "Sliding", sondern ein dreidimensionaler Prozess die bevorzugte Bewegung von EcoP15I an der DNA ist. Eine erhöhte Anzahl von Wiederholungen von CAG-Trinukleotiden (CAG-Repeats) im Exon 1 des Gens für Chorea Huntington (Huntington Disease - HD) führt zur Manifestation dieser neurodegenerativen Erkrankung. Für die Diagnostik der Erkrankung ist die exakte Bestimmung der Anzahl der CAG-Repeats von Bedeutung. Diese Arbeit zeigt die Spaltung von HD Gen Exon 1 DNA durch EcoP15I. Die halbautomatische, hoch-sensitive Analyse dieses Spaltmusters ermöglicht die exakte Bestimmung der Anzahl der CAG-Repeats. Diese Arbeit liefert den ersten Nachweis für die DNA-Translokation durch eine Typ III-Restriktionsendonuklease. Die postulierten EcoP15I-DNA-Schlaufen wurden mit Hilfe der Rasterkraftmikroskopie (SFM) abgebildet. Dadurch wird das DNA-Translokations-Modell der DNA-Spaltung durch EcoP15I bestätigt. Es werden Gemeinsamkeiten und Unterschiede des gesamten DNA-Spaltvorganges der Typ III Restriktionsendonuklease EcoP15I in bezug auf andere Restriktionsendonukleasen diskutiert. / EcoP15I is a multifunctional, hetero-oligomeric Type III restriction enzyme. Type III restriction enzymes are of general interest in medicine and functional genome analysis because they cut DNA 25 bp downstream of their recognition site. EcoP15I recognises the DNA sequence 5`-CAGCAG and needs two inverse oriented recognition sites for effective DNA cleavage. According to the present translocation collision model DNA cleavage was proposed to result from ATP dependent DNA translocation, which is expected to induce DNA loop formation, and collision of two enzyme-DNA complexes. Experiments show that EcoP15 moves rather in a three-dimensional than in a "sliding" process in search for its recognition site. Huntington''s disease (HD) is a progressive neurodegenerative disorder with autosomal-dominant inheritance. The disease is caused by a CAG trinucleotide repeat expansion located in the first exon of the HD gene. To diagnose the illness the exact determination of the number of CAG repeats is necessary. This study shows that the number of CAG repeats in the HD gene can be determined by restriction of the DNA with the endonuclease EcoP15I and subsequent high-resolution analysis of the restriction fragment pattern using the ALFexpress DNA Analysis System. Here, for the first time DNA translocation by the Type III restriction enzyme EcoP15I is demonstrated. The postulated EcoP15-DNA loops are visualised using scanning force microscopy. This confirms the translocation-collision model for DNA cleavage by EcoP15. Similarities and differences between the DNA cleavage processes of the Type III restriction enzyme EcoP15I and other restriction enzymes are discussed.