HLA and the probability of paternity.

In cases of disputed paternity, blood tests are often used to obtain an estimate of the probability that the accused male is the true father. The interpretation of the genetic data is usually based upon a statistic called the paternity index. This paper shows that the paternity index method cannot be applied to data from compound loci in the absence of information on linkage phase. Since phenotypic data from compound loci, such as HLA, MNSs, and Rh, are often useful in disputed paternity proceedings, they should be analyzed with available alternative statistics.     

The importance of HLA typing in cases of disputed paternity

In dispute paternity, the biologists must reply to two questions: 1. Is the paternity excluded or possible? 2. If it is possible, what is its probability? Valid answers can be given, using several genetic markers, among which HLA genes are specially interesting. Looking at HLA-A, B, C, DR typing of child, mother and presumed father, we propose a method which allows a direct calculation of paternity probability. Crossing over between HLA genes in presumed father and in mother are also considered in this method. In our experience, adding the date provided by the HLA genes and other genetic markers, we obtained, either formal exclusions, or possible paternities with a probability almost always higher than 90%.     

Application of the GPT system in paternity cases.

Experiments show that the GPT starch gel pattern of any given blood sample is fully reproducible, and that an individual's GPT type is constant at least after the age of 1 month. GPT isoenzyme patterns are influenced and may be changed during storage of unfrozen blood. The interval between sampling and preparation of haemolysate should therefore not exceed 4 days. In haemolysates kept at -25 degrees C the isoenzyme patterns remain unchanged for at least many months. The GPT system forms a valuable means for statistical information in paternity cases. Thus, the overall chance is 18.7% for paternity exclusion or strong evidence against paternity for a falsely alleged father. Based on a material of 1,316 paternity cases, it is concluded that the GPT system is a valuable supplement to other systems of genetic markers in cases of disputed paternity.     

On the genetics of the Pi serum proteins

Summary The authors report family studies (51 families with 134 children) on the inheritance of the Pi phenotypes. Combining these data with a Norwegian family material (77 families with 323 children) published by Fagerhol and Gedde-Dahl (1969) a total of 128 families with 457 children is now available, which allows the following conclusion: The Pi phenotypes are inherited by a simple codominant mode of heredity and they are determined by a set of (at least nine) alleles. As up to now no exception to the role of inheritance has been observed, the application of the Pi system in cases of disputed paternity seems to be discussible. Some methodological problems in connection with this are shown.Supported by the Deutsche Forschungsgemeinschaft.     

Exclusions and attributions of paternity: practical experiences of forensic genetics and statistics.

The Swedish State Institute for Blood Group Serology is a central government laboratory handling all blood typing in paternity cases in Sweden, each year testing 1,500-2,000 cases using about 13 polymorphisms. Of the accused men, 35%-40% are nonfathers, but in one-man cases (about 78% of all cases), approximately 75% are the true fathers. Exclusions appear to be distributed as expected from allele frequencies, and the paternity probability of nonexcluded men is assessed with a Bayesian approach. Some cases are retested in extended investigations which raise theoretical exclusion capability from about 87% to about 99%. Both the results of extended investigations and the theoretical consideration of the distribution of paternity probabilities support the use of such positive statistical evidence for the attribution of paternity.     

Fertility after unilateral cryptorchidism. Paternity, time to conception, pretreatment testicular location and size, hormone and sperm parameters.

OBJECTIVE: To further evaluate whether fertility is decreased among a cohort of men with previous unilateral cryptorchidism as compared with a control group of men. SUBJEcTS AND METHODS: Formerly unilateral cryptorchid men who had undergone orchiopexy between the years of 1955 and 1975 at the Children's Hospital of Pittsburgh and a control group of men who were matched for age of an unrelated surgery at the same institution were evaluated by review of medical records and by completion of a questionnaire. 359 previously cryptorchid men were identified as having attempted paternity. Of these men, 320 had information concerning preoperative testicular location and 163 for preoperative testicular size. 106 of these men had levels of testosterone, inhibin B, FSH, and LH measured, while 95 of the men had semen analyses. RESULTS: Among men who had attempted paternity, there was no statistical difference in success of paternity between the previously unilateral group (89.7%) and the control group (93.7%). There was no difference in the mean time to conception (7.1 +/- 0.7 months for the unilateral group vs. 6.9 +/- 2.3 for the control group). Within the unilateral group in regard to success at paternity, no difference was found compared with the age of orchiopexy, preoperative testicular location, or preoperative testicular size. Inhibin B levels were lower among the unilateral group. FSH, LH, testosterone, sperm density, motility and morphology were not different, but considerable variation was noted within the cryptorchid group. CONCLUSIONS: In this continued evaluation of a cohort of previously cryptorchid men who had undergone unilateral orchiopexy, paternity does not appear to be significantly compromised after unilateral cryptorchidism. Unilateral cryptorchidism appears to be one of several factors contributing to infertility, similar to those found in the general population. No correlation was found between success at paternity and the age of orchiopexy, preoperative testicular size or preoperative testicular location. Inhibin B levels were lower while FSH, LH, T and sperm parameters did not differ.     

社会性单配制鸟类婚外父权的发生和影响因素

一雌一雄单配制鸟类中,雌性个体与配偶外雄性发生交配的行为称为婚外交配,继而导致了婚外受精产生婚外子代的现象称为产生了婚外父权。婚外父权广泛存在于鸟类中,针对其发生和影响因素已经成为了鸟类行为生态学研究的热点。本文收集了近十年社会性单配制鸟类婚外父权方面的研究文献,从婚外父权的发生及其影响因素两个方面综述了单配制鸟类婚外父权的研究进展。婚外父权发生原因的探讨主要包括：1、从两性的角度探讨雌雄两性在婚外行为中不同的进化繁殖策略。雄性策略旨在增加自身的繁殖输出;有关雌性策略则提出了确保受精假说、食物供给假说、遗传利益假说等,但目前尚存争议;2、在遗传利益假说中较常见的又分为3个假说：“优秀基因”假说、“遗传相容性”假说和“遗传多样性”假说,该三种假说是针对雌性从遗传方面获得的利益而提出的,不断有报道指出雌性配偶选择会被潜在的雄性遗传特性所影响;3、非遗传利益——母系效应影响婚外父权的进化。一些研究指出遗传质量参数,如体重、身体大小、存活率和免疫应答等方面可能会存在母系效应。婚外父权发生的影响因素这里主要指环境因素,包括繁殖同步性、繁殖密度、栖息地环境、产卵及孵化时机等。由于物种不同,受到环境压力不同,导致婚外父权发生率千差万别。最后本文针对未来的研究方向做出了展望。尽管近十年的研究进一步解释了鸟类婚外父权现象,但是该领域仍然存在并且产生了许多新的未解决的问题,而相关实验操作和理论的完善是深入探讨这些问题的关键。     

应用PCR-SSOP技术研究中国汉族、维吾尔族HLA-A基因座基因多态性

人类白细胞抗原（Human Leukocyte Antigen,HLA)基因复合物位于6p21.3,有220多个不同的功能基因,是人类基因组最复杂的遗传多态系统。HLA等位基因的变异在医学、法医学、人类学等领域具有重要的意义。自从1964年以来,HLA分型一直采用经典的微量淋巴细胞毒实验,但该方法是血清学水平的分,不能识别很多特异性的等位基因,而且高质量的抗体也不易获得。从20世纪90年代起,在国家自然科学基金的资助下,首先开展HLAⅡ类位点基因分研究及大规模群体多态性调查,所获得的中国主要民族基因数据已应用于多个领域。相比之下,HLAⅠ类基因数量更丰富,包含了A、B、C、E、F、G和假基因H、J、K、L等10个位点;基因分子结构更复杂,更具多态性。因此,HLAⅠ类DNA分型比HLAⅡ类分型及行多困难。直至目前中国人群HLA－A基因座基因多态性和分布频率的研究尚未充分进行。而任何DNA标记用于遗传分析、法医鉴定等领域之前,必须先进行群体调查,建立不同民族基因数据库,这是不可逾越的基础工作。鉴于此,采用灵敏而非同位素污染的PCR－SSOP基因分型技术,对165个汉族和162个维吾尔族个体的HLA－A基因座多态性进行调查。结果在汉族群体中发现22种等位基因,频率最高的是HLA－A＊1101（19．7％）,其次是＊201（12．72％）;在维族群体中发现22种等位基因,频率最高的是＊2407（17．90％）,等位基因＊0101、＊0201和＊3301的频率均大于10％;HLA－A＊0203、＊0205、＊0302、＊2403和＊3302仅在汉族群体中检出;HLA－A＊0205、＊0211、＊2301、＊2502、＊68012和＊6802仅在维族群体中检出。按照Hardy-Weinberg平衡定律检验,两个民族各等位基因型频率的预期值与实际观察值相吻合（P＞0．05）,证明了所获得汉族、维吾尔族HLA－A位点基因频率具有可靠性;同时也表明各等位基因的遗传特征符合符合孟德尔规律。经计算机统计分析,汉族群体HLA－A基因座杂合度（Heterozygosity,H)、个体识别率（Discrimination Power,DP)和非父排排率（Proba-bility of Paternity Exclusion,EPP)分别为0．9029、0．9776和0．8592;维族群体H、DP和EEP分别为0．9063、0．9379和0．7885。和其他遗传标记（如VNTR、STR、SNP）的单一位点相比,HLA－A具有高度的杂合率、个体识别率和非父排除率。因此,HLA－A等位基因在法医个体识别、亲权鉴定、基因诊断、人类学等领域具有重要的应用价值。     

Confidence of paternity,divorce, and investment in children by Albuquerque men

Using a sample of men living in Albuquerque, NM, we examined the relationship between paternity confidence and men's investment in children. In humans, men may reduce their investment in a child in two ways: indirectly, by ending their relationship with the child's mother and ceasing to cohabit with the child (e.g., divorce), and directly, by allocating less time and fewer resources to the child. In this article, we tested two hypotheses regarding the effect of paternity confidence on investment in children: (1) men will be more likely to divorce women if they suspect or are sure that they are not the father of their wife's child, and (2) controlling for divorce, men will reduce direct investments in low paternity confidence children relative to high paternity confidence children. The first hypothesis was supported by the data. The second hypothesis was supported for two out of three measures of paternal investment we examined; low paternity confidence reduces the time men spend with a child in a group with other children or adults, and it reduces extensive involvement with the child's educational progress; there was no effect of paternity confidence on the amount of time men spend with children in one-on-one interactions. We also examined the effects of unstated paternity confidence (e.g., when men decline to answer the question) on divorce and paternal investment. Overall, the results suggested that paternity confidence plays an important role in shaping men's relationships with women and with their putative genetic children.     

Polymorphism of glyoxalase I in Vienna.

Phenotype and gene frequencies of the GLO I polymorphism in Vienna are given. No exception to the postulated rule of inheritance could be found in 23 families with 51 children and 132 mother-child pairs. Linkage with the HLA system is confirmed, but no linkage disequilibrium between GLO alleles and HLA-A, B, C genes was detected. The use of the GLO I polymorphism in paternity cases is discussed.     

Human red cell acid phosphatase polymorphism

Red cell acid phosphatase phenotypes were determined in 401 unrelated persons from Southwestern Germany. The frequencies of genes P^a, P^b and P^c were estimated to be p=0.328, q=0.630 and r=0.042.Experiences in 101 cases of disputed paternity with 151 men involved are reported. 22 men could be excluded from paternity on the basis of red cell acid phosphatase phenotypes.In all 140 mother-child-combinations tested the distribution of red cell acid phosphatase variants was compatible with the genetic model suggested by Hopkinson et al.Usefulness of the system in forensic cases of disputed paternity is discussed.Data contained in this paper will also constitute part of the thesis of cand. med. Karl-Henning Lichte.     

Allele frequency distribution of two highly polymorphic DNA sequences in three ethnic groups and its application to the determination of paternity

The allele frequency distribution of two highly polymorphic DNA sequences has been determined in three ethnic groups (American blacks, Caucasoids, and Hispanics) from the New York metropolitan area. The two loci examined were D14S1 and the flanking region of HRAS-1. The former was analyzed in EcoRI-digested DNA and the latter in TaqI-digested DNA. Approximately 700 DNA samples from unrelated individuals were digested with each of these enzymes and hybridized with the appropriate recombinant DNA probes. The size range of the DNA fragments detected for the D14S1 polymorphism varied from 14.3 to 32.5 kilobase pairs (kbp). The number of alleles identified under the experimental conditions used in this study was more than 40. For the HRAS-1 polymorphism, we have detected 18 different alleles varying in size from 1.85 to 4.5 kbp. Although the number of alleles observed in the different ethnic groups examined was very similar, the relative frequency of them varied significantly. The results presented here can be used as the basis for the utilization of DNA RFLP for the purpose of identity, such as paternity determinations or the analysis of forensic material. As an example, we have compared the results of paternity cases analyzed by HLA typing with those obtained with these two DNA polymorphisms. The values of paternity index and power of exclusion were similar by both procedures.     

Empirical validation of the Essen-Möller probability of paternity.

The validity of the Essen-Möller formulation probability of paternity is supported by demonstrating its correctness in a model genetic system--the ABO system. An analysis was made of 1,393 paternity cases typed uniformly for HLA-A and -B, ABO, Rh, and MNSs, in which the mother named one man only as the child''s father and in which both mother and putative father identified themselves as Caucasian. For purposes of analysis, putative fathers not excluded from paternity by the four systems tested were regarded as actual fathers. The joint distribution of observed triplets of ABO phenotypes is shown to be statistically consistent with expected values, and the fractions of "true" fathers for a given triplet closely approximated the probability of paternity calculated using a realistic prior probability. Recent allegations of fallaciousness of the method by Li and Chakravarty and Aickin are discussed in terms of the results presented.     

The probability of exclusion of ancestries based on genetic observations.

One can extend exclusion of ancestry beyond paternity: for example, to grandparents or other types of ancestors. Naturally, the probability of successful exclusion is smaller for more remote ancestors. The case that we have especially considered is that of exclusion on the basis of grandparents, of which there have been recent applications. A method of calculating the average probability of exclusion, P, in such situations is developed and applied to different genetic systems including DNA polymorphisms available today. As usual, multiallelic genes like HLA are by far the most informative, but a substantial number of other genes should also be tested to reach a reasonable probability of exclusion. The effect of inbreeding on P is demonstrated to be negligible.     

HLA and trisomy 21. Confirmation of a trend of restricted HLA heterogeneity in parents of Down syndrome children

As the HLA system could play a role in the in utero selection process against abnormal fetuses, HLA-A and -B antigens were evidenced in 30 children with trisomy 21 and in their parents, using a standard microlymphocytotoxicity test. The comparison group included 60 families among whom 39 had HLA typing for paternity exclusion and 21 had been previously selected for a segregation study. Both groups consisted of nonconsanguineous Caucasians from the same geographical area. The Down syndrome (DS) children did not show a significant association with a specific HLA antigen. However, six out of 30 couples having a DS child showed two antigens shared at the A and/or B locus, compared to seven out of 60 control couples. The shared parental antigens were not selectively inherited, and the proportion of homozygote children at one locus was lower for DS (5/30) than for controls (13/60). These findings demonstrate the same trend as previously published but need to be confirmed by other investigators. Perhaps a strong selective pressure in favor of heterozygotes contributes to a better survival rate, as suggested from histocompatibility studies in animals.     

Multiple paternity is related to adult sex ratio and sex determination system in reptiles

The adult sex ratio (ASR, the proportion of males in the adult population) is an emerging predictor of reproductive behaviour, and recent studies in birds and humans suggest it is a major driver of social mating systems and parental care. ASR may also influence genetic mating systems. For instance male-skewed ASRs are expected to increase the frequency of multiple paternity (defined here as a clutch or litter sired by two or more males) due to higher rates of coercive copulations by males, and/or due to females exploiting the opportunity of copulation with multiple males to increase genetic diversity of their offspring. Here, we evaluate this hypothesis in reptiles that often exhibit high frequency of multiple paternity although its ecological and life-history predictors have remained controversial. Using a comprehensive dataset of 81 species representing all four non-avian reptile orders, we show that increased frequency of multiple paternity is predicted by more male-skewed ASR, and this relationship is robust to simultaneous effects of several life-history predictors. Additionally, we show that the frequency of multiple paternity varies with the sex determination system: species with female heterogamety (ZZ/ZW sex chromosomes) exhibit higher levels of multiple paternity than species with male heterogamety (XY/XX) or temperature-dependent sex determination. Thus, our across-species comparative study provides the first evidence that genetic mating system depends on ASR in reptiles. We call for further investigations to uncover the complex evolutionary associations between mating systems, sex determination systems and ASR.     

Demographic correlates of paternity confidence and pregnancy outcomes among Albuquerque men

We examine the demographic correlates of paternity confidence, or men's assessment of the likelihood that they are the genetic father of a particular child. Evolutionary theory predicts that men will provide less parental investment for putative genetic offspring who are unlikely to be their actual offspring, but confidence of paternity has not been as extensively examined as its importance would merit. Using self-reported data on paternity confidence in 3,360 pregnancies reported by men living in Albuquerque, New Mexico, we find that low paternity confidence is more common among unmarried couples and for unplanned pregnancies. We also find that men are more likely not to state paternity confidence (i.e., they refuse to answer the question) if a pregnancy is unplanned. We additionally examine the pregnancy outcomes associated with confidence of paternity. We find that low paternity confidence pregnancies are significantly more likely to be aborted, and pregnancies for which paternity confidence is unstated are more likely to be aborted or to miscarry. Both abortion and miscarriage are associated with unmarried couples, with unplanned pregnancies, and with couples who have fewer children together.     

Ethnic differences in hepatic lipase and HDL in Japanese, black, and white Americans: role of central obesity and LIPC polymorphisms

Hepatic lipase activity (HLA) is a determinant of HDL levels, and a polymorphism in the hepatic lipase gene (LIPC) promoter (C-514T) has been hypothesized to account for higher HDL in blacks and Japanese compared with whites. To determine whether the polymorphism contributes to ethnic differences in HDL, we compared LIPC allele frequencies and HLA in Japanese American (JA; n = 84), black American (BA; n = 94), and white American (WA; n = 110) men and women. The LIPC polymorphism was associated with HLA in all cohorts (BA, P = 0.012; JA, P = 0.008; WA, P = 0.009). WA men had 49% and 58% higher HLA than BA and JA men, respectively (both P < 0.05), yet no differences in HLA were found between the women. The higher HLA in the WA men remained after adjustment for the LIPC polymorphism's effect on HLA (P = 0.037) but was erased after adjustment for waist-to-hip-ratio (P = 0.46). Although the WA men had lower HDL and HDL(3) than the JA and BA men (all P < 0.05), there were no differences in HDL(2), implying that variance in HLA may not underlie the ethnic differences in HDL levels. These results suggest that 1) the LIPC promoter polymorphism contributes to variation in HLA and HDL(2) in the three ethnic groups; 2) WA men had higher HLA than BA and JA men, related to ethnic differences in central adiposity but not LIPC allele frequency; and 3) the higher HLA in WA men did not contribute to the ethnic differences in HDL, as the differences in HDL were made up entirely of differences in HDL(3) and not HDL(2).     

Fertility after bilateral cryptorchidism. Evaluation by paternity, hormone, and semen data.

PURPOSE: Evaluation of the fertility of a cohort of formerly bilaterally cryptorchid men in comparison with a group of formerly unilaterally cryptorchid men, and a group of control men. MATERIALS AND METHODS: Using a detailed questionnaire concerning paternity and factors related to paternity, a cohort of formerly bilateral cryptorchid men were studied and compared with men who had undergone orchiopexy for unilateral cryptorchidism, and a group of control men. All study subjects had had surgery at the Children's Hospital of Pittsburgh, Pittsburgh, Pa., between 1955 and 1975. A subset of the full cohort underwent clinical evaluation that included a physical examination, serum hormonal determination and semen analyses. RESULTS: Paternity rates are significantly lower among the formerly bilaterally cryptorchid men who have attempted to father a child (65.3%) as compared to the formerly unilaterally cryptorchid (89.7%; p < 0.001) and control men (93.2%; p < 0.001). Differences in the ability to father children are also apparent when semen and hormone levels are compared between the three groups. The bilateral group has significantly lower sperm density and inhibin B levels, and higher FSH and LH levels, than the unilateral and control groups. CONCLUSIONS: Men born with bilateral cryptorchidism have severely compromised fertility in adulthood. This reduction in fertility is clearly shown in comparisons of both paternity rates, and in semen and hormone analyses, between the formerly bilateral, formerly unilateral, and control groups.     

Calculation of probability of paternity using DNA sequences.

This paper formally incorporates allele measurement error into the Essen-Möller version of the probability of paternity. For highly polymorphic genetic systems, an approximate solution to the problem is developed resulting in simple formulas. The DNA sequence of the D14S1 region provided a practical example for testing this approximation. For these sequences, allelic uncertainty arises from determining length of DNA fragments from mobility in gel electrophoresis. D14S1 and standard test results from 35 paternity cases establish the validity of our computational method.