Cardiosphere-derived cells for heart regeneration.

www.thelancet.com Vol 379 June 30, 2012 2425 2 Lemos B, Araripe LO, Hartl DL. Polymorphic Y chromosomes harbor cryptic variation with manifold functional consequences. Science 2008; 319: 91–93. 3 Lemos B, Branco AT, Hartl DL. Epigenetic eff ects of polymorphic Y chromosomes modulate chromatin components, immune response, and sexual confl ict. Proc Natl Acad Sci USA 2010; 107: 15826–31. 4 Spach KM, Blake M, Bunn JY, et al. Cutting edge: the Y chromosome controls the age-dependent experimental allergic encephalomyelitis sexual dimorphism in SJL/J mice. J Immunol 2009; 182: 1789–93. 5 Case LK, Toussaint L, Moussawi M, et al. Chromosome Y regulates survival following murine coxsackievirus B3 infection. G3 2012; 2: 115–21. reported in genome-wide association studies. However, our non-metric multidimensional scaling of autosomal SNPs from previous genome-wide association studies gives us no reason to believe that there was a systematic diff erence in the distribution of any autosomal SNPs between carriers of haplogroup I and all other lineages (supplementary fi gure 1). Additionally, the genotype distribution of rs579459 (an ABO locus SNP associated with CAD in previous genome-wide association studies) was similar between men with haplogroup I and other lineages of the Y chromosome in our analysis (supplementary table 4). Laure Case and colleagues provide an important evolutionary perspective to our fi ndings. The series of studies in fruit fl ies and rodents clearly shows that the Y chromosome is an important regulator of immunity and a potential contributor to autoimmune diseases in experimental models. The question as to whether the eff ect of the Y chromosome on cardiovascular disease is mediated by its euchromatin (through proteincoding genes), its heterochromatin (through epigenetic mechanism), or a combination of both is intriguing and requires further studies.