The human serine protease inhibitor (serpin) gene cluster at 14q32.1 is a useful model system for studying the regulation of gene activity and chromatin structure. We demonstrated previously that the six known serpin genes in this region were organized into two subclusters of three genes each that occupied approximately 370 kb of DNA. To more fully understand the genomic organization of this region, we annotated a 1-Mb sequence contig from data from the Genoscope sequencing consortium (http://www.genoscope.cns.fr/ ). We report that 11 different serpin genes reside within the 14q32.1 cluster, including two novel alpha1-antiproteinase-like gene sequences, a kallistatin-like sequence, and two recently identified serpins that had not been mapped previously to 14q32.1. The genomic regions proximal and distal to the serpin cluster contain a variety of unrelated gene sequences of diverse function. To gain insight into the chromatin organization of the region, sequences with putative nuclear matrix-binding potential were identified by using the MAR-Wiz algorithm, and these MAR-Wiz candidate sequences were tested for nuclear matrix-binding activity in vitro. Several differences between the MAR-Wiz predictions and the results of biochemical tests were observed. The genomic organization of the serpin gene cluster is discussed.

DNA evidence has transformed the proof of identity in criminal litigation, but it has also introduced daunting problems of statistical analysis into the process. In this Article, we analyze a problem related to DNA evidence that is likely to be of great and increasing significance in the near future. This is the problem of whether, and how, to present evidence that the suspect has been identified through a DNA database search. In our view, the two well-known reports on DNA evidence issued by the National Research Council ("NRC"), each of which has carried great authority with the American courts on various issues, have been badly mistaken in their analysis of this problem. Similar errors affect the analyses of scholars who have supported the NRC reports. We will also offer some reflections on the habits of mind, of both lawyers and statisticians, that may have led to this result. Finally, we will suggest an approach that legal decisionmakers might take in general with respect to scientific and statistically-based evidence to avoid this kind of difficulty. This approach is significantly different from that which pervades the Supreme Court's decisions in Daubert v. Merrell Dow Pharmaceuticals, Inc. 1 and its recent sequel, General Electric Co. v. Joiner, 2 as well as their precursor, Frye v. United States. 3 And the

This essay responds to D. Davis and W. C. Follette (2002), who question the value of motive evidence in murder cases. They argue that the evidence that a husband had extramarital affairs, that he heavily insured his wife's life, or that he battered his wife is ordinarily of infinitesimal probative value. We disagree. To be sure, it would be foolish to predict solely on the basis of such evidence that a husband will murder his wife. However, when this kind of evidence is combined with other evidence in a realistic murder case, the evidence can be quite probative. We analyze cases in which it is virtually certain that the victim was murdered but unclear who murdered her, and in which it is uncertain whether the husband murdered the wife or she died by accident. We show that in each case motive evidence, such as a history of battering or of infidelity, can substantially increase the odds of the husband's guilt. We also consider the actual case on which Davis and Follette base their paper. We argue that testimony of Davis on the basis of the analysis presented in their paper was properly excluded, for it would have been misleading and unhelpful.

BackgroundParental consanguinity is a risk factor for congenital heart disease (CHD) worldwide, suggesting that a recessive inheritance model may contribute substantially to CHD. In Bangalore, India, uncle-niece and first cousin marriages are common, presenting the opportunity for an international study involving consanguinity mapping of structural CHD. We sought to explore the recessive model of CHD by conducting a genome-wide linkage analysis utilizing high-density oligonucleotide microarrays and enrolling 83 CHD probands born to unaffected consanguineous parents.Methodology/Principal FindingsIn this linkage scan involving single nucleotide polymorphism (SNP) markers, the threshold for genome-wide statistical significance was set at the standard log-of-odds (LOD) score threshold of 3.3, corresponding to 1995∶1 odds in favor of linkage. We identified a maximal single-point LOD score of 3.76 (5754∶1 odds) implicating linkage of CHD with the major allele (G) of rs1055061 on chromosome 14 in the HOMEZ gene, a ubiquitously expressed transcription factor containing leucine zipper as well as zinc finger motifs. Re-sequencing of HOMEZ exons did not reveal causative mutations in Indian probands. In addition, genotyping of the linked allele (G) in 325 U.S. CHD cases revealed neither genotypic nor allele frequency differences in varied CHD cases compared to 605 non-CHD controls.Conclusions/SignificanceDespite the statistical power of the consanguinity mapping approach, no single gene of major effect could be convincingly identified in a clinically heterogeneous sample of Indian CHD cases born to consanguineous parents. However, we are unable to exclude the possibility that noncoding regions of HOMEZ may harbor recessive mutations leading to CHD in the Indian population. Further research involving large multinational cohorts of patients with specific subtypes of CHD is needed to attempt replication of the observed linkage peak on chromosome 14. In addition, we anticipate that a targeted re-sequencing approach may complement linkage analysis in future studies of recessive mutation detection in CHD.