Identification Strategy of Biological Half Sibling Relationship / 法医学杂志

OBJECTIVES@#To compare the application value of the likelihood ratio (LR) method and identity by state (IBS) method in the identification involving half sibling relationships, and to provide a reference for the setting of relevant standards for identification of half sibling relationship.@*METHODS@#(1) Based on the same genetic marker combinations, the reliability of computer simulation method was verified by comparing the distributions of cumulated identity by state score (CIBS) and combined full sibling index in actual cases with the distributions in simulated cases. (2) In different numbers of three genetic marker combinations, the simulation of full sibling, half sibling and unrelated individual pairs, each 1 million pairs, was obtained; the CIBS, as well as the corresponding types of cumulative LR parameters, were calculated. (3) The application value of LR method was compared with that of IBS method, by comparing the best system efficiency provided by LR method and IBS method when genetic markers in different amounts and of different types and accuracy were applied to distinguish the above three relational individual pairs. (4) According to the existing simulation data, the minimum number of genetic markers required to distinguish half siblings from the other two relationships using different types of genetic markers was estimated by curve fitting.@*RESULTS@#(1) After the rank sum test, under the premise that the real relationship and the genetic marker combination tested were the same, there was no significant difference between the simulation method and the results obtained in the actual case. (2) In most cases, under the same conditions, the system effectiveness obtained by LR method was greater than that by IBS method. (3) According to the existing data, the number of genetic markers required for full-half siblings and half sibling identification could be obtained by curve fitting when the system effectiveness reached 0.95 or 0.99.@*CONCLUSIONS@#When distinguishing half sibling from full sibling pairs or unrelated pairs, it is recommended to give preference to the LR method, and estimate the required number of markers according to the identification types and the population data, to ensure the identification effect.

Equation Derivation of the Probability Distribution of IBS Score among Full Sibling Pairs / 法医学杂志

Objective To derive the general equation of the probability distribution of identity by state （IBS） score among biological full sibling pairs by calculating STR allele frequency. Methods Based on the Mendelian genetics law and the hypothesis that parents of biological full siblings （FS） were unrelated individuals, the IBS score and corresponding probability of different genotype combinations in the offspring when unrelated individuals of different genotype combinations give birth to two offsprings were derived. Results Given fi （i=1, 2, …, m） as the frequency of the ith allele of a STR locus, the probability of sharing 2 alleles （p2FS）, 1 allele （p1FS） or 0 allele （p0FS） with biological full sibling pairs on the locus can be respectively expressed as follows： (see the text). The sum of p2FS, p1FS and p0FS must be 1. As for the multiple genotyping system that contained n STR loci, IBS scores between biological full sibling pairs conform to binomial distribution： IBS~B（2n, π1）. The population rate π1, can be given by the formula： (see the text). Conclusion The alternative hypothesis in biological full sibling testing is that two appraised individuals are biological full siblings. The probability of the corresponding alternative hypothesis of any STR locus combination or IBS score can be directly calculated by the equations presented in this study, and the calculation results are the basis for explanations of the evidence.

Formula Derivation for the Probability Distribution of IBS Score in Unrelated Individual Pairs / 法医学杂志

OBJECTIVES@#To derive the probability equation given by STR allele frequencies of identity by state （IBS） score shared by unrelated individual pairs.@*METHODS@#By comparing the STR genotypes of two unrelated individuals, three mutually exclusive combinations could be obtained： （1） sharing 2 identical alleles, a₂=1, otherwise a₂=0; （2） sharing 1 identical allele, a₁=1, otherwise a₁=0; （3） sharing 0 identical allele, a₀=1, otherwise a₀=0. And the IBS score of the one STR locus in this unrelated individual pair could be given by the formula： ibs=2a₂+a₁. The probability of a₂=1 （p₂）, a₁=1 （p₁） and a₀=1 （p₀） were derived and expressed in powers of the allele frequencies. Subsequently, for a genotyping system including n independent STR loci, the characteristics of binomial distribution of IBS score shared by a pair of unrelated individuals could be given by p₂l and p₁l （l=1, 2, …, n）.@*RESULTS@#All the general equations of p₂, p₁ and p₀ were derived from the basic conceptions of a₂, a₁ and a₀, respectively. Given fi （i=1, 2, …, m） as the ith allele frequency of a STR locus, the general equations of p₂, p₁ and p₀ could be respectively expressed in powers of fi： [Formula: see text],[Formula: see text] and [Formula: see text]. The sum of p₂, p₁ and p₀ must be equal to 1. Then, the binomial distribution of IBS score shared by unrelated individual pairs genotyped with n independently STR loci could be written by： IBS~B（2n, π）, and the general probability, π, could be given by the formula： [Formula: see text].@*CONCLUSIONS@#In the biological full sibling identification, the probability of null hypothesis corresponding to any specific IBS score can be directly calculated by the general equations presented in this study, which is the basement of the evidence explanation.

Full Sibling Identification by IBS Scoring Method and Establishment of the Query Table of Its Critical Value / 法医学杂志

OBJECTIVES@#To establish a query table of IBS critical value and identification power for the detection systems with different numbers of STR loci under different false judgment standards.@*METHODS@#Samples of 267 pairs of full siblings and 360 pairs of unrelated individuals were collected and 19 autosomal STR loci were genotyped by Goldeneye™ 20A system. The full siblings were determined using IBS scoring method according to the 'Regulation for biological full sibling testing'. The critical values and identification power for the detection systems with different numbers of STR loci under different false judgment standards were calculated by theoretical methods.@*RESULTS@#According to the formal IBS scoring criteria, the identification power of full siblings and unrelated individuals was 0.764 0 and the rate of false judgment was 0. The results of theoretical calculation were consistent with that of sample observation. The query table of IBS critical value for identification of full sibling detection systems with different numbers of STR loci was successfully established.@*CONCLUSIONS@#The IBS scoring method defined by the regulation has high detection efficiency and low false judgment rate, which provides a relatively conservative result. The query table of IBS critical value for identification of full sibling detection systems with different numbers of STR loci provides an important reference data for the result judgment of full sibling testing and owns a considerable practical value.

Influencia del polimorfismo genético rs2927488 de Bcl3 en el síndrome de intestino irritable / Influence of genetic polymorphism rs2927488 of the Bcl3 irritable bowel syndrome

Irritable Bowel Syndrome (IBS) is a functional disorder characterized by abdominal discomfort associated with changes in bowel habit and increased intestinal sensitivity. It is one of the most common disorders of digestive health in Chile as well as in the world. Although the pathophysiological mechanisms of IBS have yet to be fully established, it is known that (epi-) genetic factors are involved in the development of the disorder. Bcl3 (B-cell leukemia/lymphoma 3) is a regulatory protein of the intestinal inflammatory response, specifically, with regard to the signaling pathways of NF-kB (Nuclear Factor-kB). Among the variability of the human genome, the gene encoding Bcl3 contains the polymorphism SNPs rs2927488 (variants A/G) which has been associated with susceptibility to developing Inflammatory Bowel Disease (IBD). Furthermore, the presence of this polymorphic variant has been correlated with increased levels of Bcl3 gene expression in patients with Crohn’s Disease. Our laboratory is focused on understanding the potential relationship between Bcl3 and IBS. Our preliminary studies describe an increased expression of Bcl3 at the intestinal mucosal epithelium in IBS patients with a diarrheal-phenotype (IBS-D). We are now interested to investigate if the presence of the variant SNP rs2927488(A/G) is a susceptibility factor for IBS development and to understand the significance of its relationship with Bcl3 expression, in Chilean IBS patients. In this review, we focus primarily on the relationship between rs2927488(A/G) polymorphism of Bcl3 gene, its protein expression and its mechanisms of control over the inflammatory response...

Serotonin Transporter Gene Polymorphism in Healthy Adults and Patients with Irritable Bowel Syndrome / 대한소화기학회지

BACKGROUND/AIMS: Serotonin is thought to be an important neurotransmitter in the pathogenesis of irritable bowel syndrome (IBS). It is reported that functional polymorphism in the promotor region of the serotonin transporter gene is related with the subtypes of IBS and shows racial difference. However, a functional relation between polymorphism and IBS is not clear. The aim of this study was to investigate 5-hydroxytryptamine transporter (5-HTT) gene polymorphism in patients with IBS. METHODS: For fifty-six healthy controls and 33 patients with IBS fulfilling Rome II criteria, 5'-flank promotor region of 5-HTT gene was analyzed by polymerase chain reaction. RESULTS: The genotypes of healthy controls were S/S (57.1%), S/L (37.5%), and L/L (5.4%). Those of IBS patients were S/S (54.5%), S/L (36.4%), and L/L (9.1%). IBS patients were divided into three groups: diarrhea predominant (n=15; S/S, 40%; S/L, 53.3%; L/L, 6.7%), constipation predominant (n=12; S/S, 75.0%; S/L, 8.3%; L/L, 16.7%), diarrhea-constipation alternating type (n=6; S/S, 50%; S/L, 50%). There was no statistical difference in the 5-HTT gene polymorphism between patients and controls, and according to the subtypes of IBS patients (p=0.135). CONCLUSIONS: There was no relationship between serotonin transporter gene polymorphism and IBS. However, allele S/S genotype was most prominent genotype in both controls and patients.