Atrial fibrillation (AF) is a common cardiac arrhythmia whose molecular etiology is poorly understood. We studied a family with hereditary persistent AF and identified the causative mutation (S140G) in the KCNQ1 (KvLQT1) gene on chromosome 11p15.5. The KCNQ1 gene encodes the pore-forming alpha subunit of the cardiac I(Ks) channel (KCNQ1/KCNE1), the KCNQ1/KCNE2 and the KCNQ1/KCNE3 potassium channels. Functional analysis of the S140G mutant revealed a gain-of-function effect on the KCNQ1/KCNE1 and the KCNQ1/KCNE2 currents, which contrasts with the dominant negative or loss-of-function effects of the KCNQ1 mutations previously identified in patients with long QT syndrome. Thus, the S140G mutation is likely to initiate and maintain AF by reducing action potential duration and effective refractory period in atrial myocytes.

A main task in condensed-matter physics is to recognize, classify, and characterize phases of matter and the corresponding phase transitions, for which machine learning provides a new class of research tools due to the remarkable development in computing power and algorithms. Despite much exploration in this new field, usually different methods and techniques are needed for different scenarios. Here, we present SimCLP: a simple framework for contrastive learning phases of matter, which is inspired by the recent development in contrastive learning of visual representations. We demonstrate the success of this framework on several representative systems, including non-interacting and quantum many-body, conventional and topological. SimCLP is flexible and free of usual burdens such as manual feature engineering and prior knowledge. The only prerequisite is to prepare enough state configurations. Furthermore, it can generate representation vectors and labels and hence help tackle other problems. SimCLP therefore paves an alternative way to the development of a generic tool for identifying unexplored phase transitions.

A partial physical map has been constructed of the human class Mu glutathione S-transferase genes on chromosome 1p13.3. The glutathione S-transferase genes in this cluster are spaced about 20 kilobase pairs (kb) apart, and arranged as 5 -GSTM4-GSTM2-GSTM1-GSTM5-3 . This map has been used to localize the end points of the polymorphic GSTM1 deletion. The left repeated region is 5 kb downstream from the 3 -end of the GSTM2 gene and 5 kb upstream from the beginning of the GSTM1 gene; the right repeated region is 5 kb downstream from the 3 -end of the GSTM1 and 10 kb upstream from the 5 -end of the GSTM5 gene. The GSTM1-0 deletion produces a novel 7.4-kb HindIII fragment with the loss of 10.3-and 11.4-kb HindIII fragments. The same novel fragment was seen in 13 unrelated individuals (20 null alleles), suggesting that most GSTM1-0 deletions involve recombinations between the same two regions. We have cloned and sequenced the deletion junction that is produced at the GSTM1-null locus; the 5 -and 3 -flanking regions are more than 99% identical to each other and to the deletion junction sequence over 2.3 kb. Because of the high sequence identity between the left repeat, right repeat, and deletion junction regions, the crossing over cannot be localized within the 2.3-kb region. The 2.3-kb repeated region contains a reverse class IV Alu repetitive element near one end of the repeat.The glutathione S-transferases (EC 2.5.1.18) are a superfamily of catalytic and binding proteins that detoxify chemical carcinogens (1). Based primarily on protein sequence similarity, the soluble glutathione S-transferases have been divided into four protein families: classes Alpha, Mu, Pi, and Theta. Class Alpha and Mu families typically contain four or more members in mammalian genomes. In humans, a large fraction of the population carries polymorphic deletions for the class Mu GSTM1 gene (about 50% of the population is homozygous GSTM1-null; Ref. 2) and the class Theta GSTT1 gene (40% of the population is homozygous GSTT1-null; Ref. 3).Significant associations between the GSTM1-0 deletion and increased cancer incidence in case/control studies have been reported for lung (4 -6), bladder (7,8), and skin cancer (9 -11). Both positive and negative results have been reported for associations between GSTM1-0 and cancer risk. A large study (6) on the effect of the GSTM1 deletion and lung cancer among caucasians and African Americans in southern California suggests that, in these populations at least, the association of the GSTM1-0 deletion and cancer is not strong. London et al. (6) found a significant association between lung cancer and the GSTM1 deletion only in cancer patients with a history of smoking but who had smoked less than 40 pack-years (e.g. 2 packs/ day for 20 years) (odds ratio ϭ 1.77, 95% CI 1 ϭ 1.11-2.82). After regression to remove age, sex, and smoking history effects, no significant association was found for total lung cancer cases or for cases where the patient had smoked more than 40 pack-years. These authors reviewed the lit...

Psoriasis is a heterogeneous disease with seven major psoriasis susceptibility loci reported so far on chromosomes 1p, 1q, 3q, 4q, 6p, 17q, and 19p, respectively. To investigate the psoriasis susceptibility loci in Chinese Hans, a genome-wide scan was performed with two-point and multipoint parametric and nonparametric linkage analyses in 61 multiplex families. These families were Chinese Hans residing in east and south-east China, comprising 189 affected and 166 unaffected individuals. We detected evidence for linkage at 6p21 (PSORS1) with nonparametric linkage scores > 3 in the range of 39.9-62.3 cM and a maximum multipoint nonparametric linkage score of 4.58 (p=0.000032). Parametric analysis revealed a maximum two-point heterogeneity lod score of 4.30 with 58% as the proportion of linked families (alpha) and a maximum multipoint heterogeneity lod score of 4.25 (alpha=53%) under the assumption of a dominant model. We could not confirm a previous reported locus (PSORS3) on distal chromosome 4q; however, a region of highly suggestive linkage was identified proximal to this proposed locus. Multipoint nonparametric analysis demonstrated nonparametric linkage scores > 3 throughout a region between 152.5 cM and 165.1 cM (from pter) with a maximum peak of 3.69 (p=0.00033) at 157.9 cM, which locates D4S413. A maximum multipoint heterogeneity lod score of 2.31 (alpha=46%) was reached at 163.1 cM. With two-point parametric linkage analysis, we observed the highest lod score of 2.43 and heterogeneity lod score of 3.94 (alpha=77%) at marker D4S1597. Our results showed that chromosomes 6p and 4q may contain genes involved in the susceptibility to psoriasis vulgaris in a Chinese Han population. Other regions with weaker evidence for linkage could also hide minor susceptibility genes.

Dyschromatosis symmetrica hereditaria is a rare autosomal dominant cutaneous disorder characterized by a mixture of hyperpigmented and hypopigmented macules of various sizes on the face and the dorsal aspects of the extremities. The genetic basis for this disease is unknown. We performed a genome-wide search in two large Chinese families to map the chromosome location of the responsible gene. We identified a locus at chromosome 1q11-1q21 with a cumulative maximum two-point LOD score of 8.85 at marker D1S2343 (at recombination fraction=0.00). Haplotype analyses indicated that the disease gene is located within the 11.6 cM region between markers D1S2696 and D1S2635. This is the first locus identified for dyschromatosis symmetrica hereditaria. This study provides a map location for isolation of a disease gene causing dyschromatosis symmetrica hereditaria.