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Pseudo-exclusion from paternity due to maternal uniparental disomy 16.

The investigation of a case of disputed paternity revealed indirect exclusion of the alleged father in the haptoglobin system and in the DNA single-locus system D16S309/Hinf I (MS205). The paternity index for the non-exclusion systems was > 10(6). Since both exclusion systems (HP and MS205) are located on chromosome 16, we investigated 10 microsatellite loci covering this chromosome with 10-20 cM resolution. Analysis of the child's chromosome showed only alleles of maternal origin and lack of inheritance of paternal alleles for five informative loci. The markers close to the centromere of chromosome 16 were heterozygous, whereas distal loci were either heterozygous or homozygous for maternal alleles. This is consistent with a maternal meiosis I nondisjunction of chromosome 16 leading to maternal uniparental heterodisomy. This case emphasizes that the opinion of non-paternity should be based on the absence of paternal alleles at genetic systems located on at least two different chromosomes.

Alleles↗

Paternal origin of FGFR3 mutations in Muenke-type craniosynostosis.

Muenke syndrome, also known as FGFR3-associated coronal synostosis, is defined molecularly by the presence of a heterozygous nucleotide transversion, c.749C>G, encoding the amino acid substitution Pro250Arg, in the fibroblast growth factor receptor type 3 gene (FGFR3). This frequently occurs as a new mutation, manifesting one of the highest documented rates for any transversion in the human genome. To understand the biology of this mutation, we have investigated its parental origin, and the ages of the parents, in 19 families with de novo c.749C>G mutations. All ten informative cases originated from the paternal allele (95% confidence interval 74-100% paternal); the average paternal age at birth overall was 34.7 years. An exclusive paternal origin of mutations, and increased paternal age, were previously described for a different mutation (c.1138G>A) of the FGFR3 gene causing achondroplasia, as well as for mutations of the related FGFR2 gene causing Apert, Crouzon and Pfeiffer syndromes. We conclude that similar biological processes are likely to shape the occurrence of this c.749C>G mutation as for other mutations of FGFR3 as well as FGFR2.

Adult↗

Quantification of the paternal allele bias for new germline mutations in the retinoblastoma gene.

New germline mutations in the human retinoblastoma gene are known to arise preferentially on paternally derived chromosomes, but the magnitude of that bias has not been measured. We evaluated 49 cases with a new germline mutation and found that in 40 cases (82%) the mutation arose on the paternally derived allele. We also evaluated 48 cases likely to have a somatic initial mutation; in this group the initial mutation arose on paternal or maternal chromosomes with approximately equal frequency. There was no statistically significant difference in the average age of fathers of children with new paternal germline mutations from the average age of fathers of children with new maternal germline mutations or somatic initial mutations. Combining the data with that from previous reports from other groups, the proportion of new germline mutations arising on a paternally derived allele is 85% (based on 72 cases; 95% confidence interval = 76-93%). This number can be useful in the genetic counseling of some families with retinoblastoma.

Adult↗

Cohabitation alters vasopressin innervation and paternal behavior in prairie voles (Microtus ochrogaster).

The density of vasopressin-immunoreactive (AVP-ir) fibers in the lateral septum and lateral habenular nucleus is lower in prairie vole fathers--which display paternal behavior under natural conditions-than in sexually naive males. To see if these changes occur before or after the birth of pups, and whether they are related to changes in paternal behavior, we tested paternal responsiveness and measured AVP-ir fiber density in the lateral septum, lateral habenular nucleus, medial preoptic area, and paraventricular nucleus of the thalamus of sexually naive males and females (0P) and breeding pairs that were sacrificed shortly after mating (3P); during early (13P); or late gestation (21P); or after the birth of pups (6PP). Paternal responsiveness was increased in 3P males and reached a plateau in 13P males. AVP-ir fiber density did not change in the medial preoptic area and the paraventricular nucleus of the thalamus. The fiber density in the lateral septum and lateral habenular nucleus was affected differently in males and females. Among males, 3P animals had the lowest fiber density, while 13P and 6PP animals had an intermediate, and 0P and 21P animals the highest fiber density, whereas among females, no differences in fiber density were found. A second experiment showed that the decrease in fiber density in 3P males could be induced by cohabitation with an unfamiliar female but not by an unfamiliar male nor by relocation to a novel cage. The changes in AVP-ir fiber density shortly after mating suggest that these fibers may be involved in paternal responsiveness as well as in various other social behaviors that change after mating.

Amygdala↗

On the theory and practice of Essen-Möller's W value and Gürtler's paternity index (PI).

In cases of disputed parentage the biostatistical information is contained in the frequencies X and Y (as defined by Essen-M oller ); X denotes the hypothesis "paternity", Y the hypothesis "non-paternity". Essen-M oller proposed a probability of paternity which includes both values: W = X/(X + Y) (where X + Y becomes 1). G urtler recommends the ratio X/Y as a "Paternity Index" (= PI). Both W and PI are based on a neutral prior probability (= 0.5 in normal triplet cases) and contain the same information, though differing in form. It is this difference which can lead to different results in forensic practice. W% is the common form for expressing probabilities, and each range of W values has an appropriate, easily understood verbal predicate . By contrast, the PI value is more abstract and can be interpreted as providing fixed decision limits, a possibility increased by the lack of distinct subdivisions with verbal predicates . Tables and computer programs are available for calculating W values even in complex cases. If one chooses to use PI values instead of W they must be calculated by the following formula: (formula; see text) Calculations become complicated where more than two hypotheses are involved, as e.g. in cases involving several men ("multi-men cases"). The author cannot find any arguments for preferring PI to W. Accordingly, he recommends the use of the W value and not the Paternity Index in biostatistical evaluations of blood group findings in cases of disputed parentage.

Aged↗

Biostatistical parameters of paternity and calculation by a computer programme.

Biostatistical Parameters such as the paternal markers in the child (PM), individual exclusion change (IEC) probability of incidental involvement (Z), probability of paternity (POP), plausibility of paternity according to Essen-M oller ( PLEM ) and paternity index (PI) are defined and discussed in respect to their application in cases of disputed paternity. In order to calculate these parameters for up to 24 marker systems, including HLA under strict observation of the linkage disequilibrium, a computer programme in BASIC has been developed.

Blood Group Antigens↗

Paternity testing with oligonucleotide multilocus probe (CAC)5/(GTG)5: a multicenter study.

The statistical analysis is reported of 256 paternity cases referred to seven different German laboratories for multilocus DNA fingerprinting with oligonucleotide probe (CAC)5/(GTG)5 and restriction enzyme HinfI. All parameters characteristic of multilocus DNA fingerprints were found to differ significantly between the contributing centres: the number of analyzed gel positions, the number of bands scored per individual, the probability of occurrence of a band at a particular position, and the band-sharing probabilities between the mother and both child and alleged father. Despite these differences, paternity cases could be divided clearly into two distinct subgroups on the basis of (i) offspring bands that could not be assigned to either the mother or the alleged father and (ii) the extent of band-sharing between child and alleged father. This partitioning, which is likely to correspond to true and false paternity, confirms previous findings for other multilocus probes. A goodness-of-fit test on the normalized number of bands scored per individual revealed no systematic deviations from commonly adopted analytical models regarding electrophoretic bands as independent entities. Log10-likelihood ratios of paternity vs. non-paternity were calculated utilizing one of these models, and a clear-cut partitioning was again obtained which coincides with that mentioned before. Only one case could not be decided unambiguously, and was either due to two independent mutations or to a close relative of the alleged father being the true father.

Child↗

Possible pitfalls in motherless paternity analysis with related putative fathers.

Nowadays, more and more paternity cases are carried out investigating only child and putative father, mostly for economical or private reasons. Usually, reliable results can be obtained and the putative father can be included or ruled out with a high certainty. Considerable problems might arise when a relative of the biological father is investigated as being the putative father. In this study, we investigated 164 persons from 27 families creating artificial deficiency cases using the AmpFlSTRIdentifiler kit, which amplifies 15 STRs simultaneously. We analyzed 93 child/biological father pairs and the corresponding uncles, respectively the brothers of the biological fathers. The average paternity probability for the biological father was 99.9699% (paternity index (PI): 3321.26); only in three cases the results were under 99.9%. In five out of 125 child/uncle pairs no STR mismatches were found and paternity probabilities between 99.9726% (PI 3652) and 99.9970% (PI 33,545) were calculated. The average number of excluding loci was 3.4, but in 31.2% of the cases only zero, one or two mismatches were found. When both putative fathers were genetically typed, the biological father usually had a statistically higher paternity probability. Nevertheless, the differences between probabilities for father and uncle were only small. These results show that a reliable investigation of deficiency cases (i.e. child and putative father) seems to be more difficult than generally assumed. Especially in cases with an unknown familiar background and/or when investigating foreigners for immigration purposes, the laboratory expert should include the mother, increase the number of investigated loci or include a second method such as RFLP-analysis, some serological systems or typing of X-chromosome specific STRs to further ascertain the results.

Adult↗

Comparative analysis of male androgen responsiveness to social environment in birds: the effects of mating system and paternal incubation.

Male androgen responses to social challenges have been predicted to vary with mating system, male-male aggressiveness, and the degree of paternal investment in birds ("challenge hypothesis," Am. Nat. 136 (1990), 829). This study focused on the interspecific predictions of the challenge hypothesis. Comparative methods were used to control for effects of the phylogenetic relatedness among the sampled species. Male androgen data of 84 bird species were collected from literature records on seasonal androgen patterns. From these, the androgen responsiveness (AR) was calculated as described in the original challenge hypothesis (i.e., maximum physiological level/breeding baseline). Scatterplots of AR versus mating strategy, male-male aggressiveness, and the degree of paternal care confirmed the expected interspecific patterns. When phylogenetic analyses were performed among all of the sampled species, the effects of paternal investment disappeared while the AR remained covarying to a high degree with mating system and male-male aggressiveness. Although these mechanisms may be different at the intraspecific level, this suggests that interspecific differences of AR in male birds may have evolved in response to changes of mating strategies, rather than in response to altered paternal duties. However, control for phylogeny among the subsample of 32 passerine species revealed that if any paternal investment contributed to the observed variance in AR, then the change from "no male incubation" to "male shares incubation duties" represented the most effective, whereas the male's contribution to feeding offspring did not explain the observed variation of AR.

Aggression↗

Risk factors for adult paternity in births to adolescents.

OBJECTIVE: To examine the risk factors for adult (aged 20 years and older) paternity in births to teenagers (14-17 years of age). METHODS: This was a population-based, retrospective cohort analysis of 27,215 adolescent mothers residing in California who had a live singleton birth during 1993. Adjusted risks for adult paternity by paternal and maternal characteristics were derived from comparisons of adult-teen and teen-teen couples. RESULTS: Adult fathers, who were responsible for 49.2% of births to teenage mothers, were a mean of 6.4 years older than the mother. The most important risk factors for adult paternity were as follows: father's (odds ratio [OR] 5.19; 95% confidence interval [CI] 4.43, 6.08) or mother's (OR 1.33; 95% CI 1.14, 1.55) educational attainment of at least 3 years lower than expected for their age, two or more previous live births (OR 3.34; 95% CI 2.48, 4.53), mother's birthplace outside the United States (OR 2.33; 95% CI 2.11, 2.58), father's (OR 2.16; 95% CI 1.98, 2.36) or mother's (OR 1.28; 95% CI 1.15, 1.42) educational attainment 1-2 years lower than expected for their age, one previous live birth (OR 1.92; 95% CI 1.75, 2.12), and Asian (OR 1.29; 95% CI 1.04, 1.62) or African American race (OR 1.25; 95% CI 1.06, 1.46) of the father. CONCLUSIONS: Teenage pregnancy prevention programs must address adult paternity, which contributed to almost half of the births in our study. These programs should consider education adequacy, cultural beliefs and practices, previous live births, and race and ethnicity when designing programs to decrease the number of adults involved in teenage births.

Adolescent↗

Demographic characteristics in adult paternity for first births to adolescents under 15 years of age.

PURPOSE: To examine parental demographic characteristics by adult (> or = 20 years at baby's conception) and teenage (< 20 years at baby's conception) paternity in births to very young adolescents (< 15 years at baby's conception). METHODS: This was a population-based, retrospective cohort analysis of all 12,317 very young adolescent mothers residing in California with a first singleton live birth during 1993-1995. Risks for adult, compared to teenage, paternity were evaluated using multivariate logistic regression. RESULTS: Adult fathers, responsible for 26.7% of births to very young adolescents, were a mean of 8.8 years older than the mother. The risk factors for adult compared to adolescent paternity were as follows: father's educational attainment of at least 3 years below that considered adequate for his age [adjusted odds ratio (AOR) = 8.34], father's (AOR = 2.46) or mother's (AOR = 1.36) educational attainment 1-2 years below that considered adequate for their age, mother's birthplace outside the United States (AOR = 3.12), and father's Hispanic ethnicity (AOR = 1.60) or African-American race (AOR = 1.50). CONCLUSIONS: Adult fathers were responsible for over one quarter of the births in our study. Adolescent pregnancy prevention focusing on younger adolescents must programmatically address adult paternity. Variations in adult paternity patterns across cultural groups suggest that we need further study of the role that cultural beliefs and practices play in very young adolescent pregnancy.

Adolescent↗

Paternity probability when a relative of the father is an alleged father.

When scientists use DNA evidence in court, coancestry effects such as population structure and relatedness are usually ignored. In paternity cases, only if a particular man has the child's paternal allele at a certain locus, can he not be excluded in the paternity dispute. However, it is certainly true that close relatives will be far more likely to have the child's paternal allele than will random members of the reference population. In particular, the probability that the true father's brother has the paternal allele is very much greater than that for any other relationship. In this paper, the authors describe a method for inference in a case where the true father may be a relative of the alleged father. This paper also reports that most current methods overstate the probability that the alleged father is the father.

Alleles↗

Male reproductive success in a promiscuous mammal: behavioural estimates compared with genetic paternity.

Molecular techniques have enabled behavioural ecologists to reassess mating systems from a genetic perspective. Studies of paternity frequently reveal that mating behaviour does not always reflect parentage, and may bring to light alternative mating tactics. Here we present a comparison of behavioural and genetic measures of male reproductive success in a mammalian mating system in which both sexes are highly promiscuous. Rather than having a stable harem social structure, Soay rams (Ovis aries) on the island of Hirta, St Kilda, UK usually consort with individual oestrous ewes sequentially. Not all matings occur between consort pairs, however, and ewes have been seen to mate with up to 10 different rams on the same day. Using locus-specific polymorphism at five protein and 10 microsatellite DNA loci, we determined paternity for 236 lambs born into three cohorts, and compared paternity with estimates of mating success derived from more than one census of rutting behaviour. The correlation between the number of ewes with which each ram was witnessed in consort and the number of paternities assigned was positive and statistically significant, and rams that were observed in consort with a ewe were 18 times more likely to have sired her offspring than other candidate rams. However, most lambs (73%) were not sired by a ram seen in consort with the oestrous mother. Many juveniles, yearlings and some adult rams were rarely seen in consort with ewes, yet were assigned a significant number of paternities. These results suggest that mating tactics differ between age groups, and that alternative mating strategies among adults that do not involve forming consorts with many females also confer mating success. For these reasons, census-based observations of consort associations between individuals cannot be used to accurately estimate individual male reproductive success in this population.

Animals↗

A retrospective assessment of the accuracy of the paternity inference program CERVUS.

CERVUS is a Windows-based software package written to infer paternity in natural populations. It offers advantages over exclusionary-based methods of paternity inference in that multiple nonexcluded males can be statistically distinguished, laboratory typing error is considered and statistical confidence is determined for assigned paternities through simulation. In this study we use a panel of 84 microsatellite markers to retrospectively determine the accuracy of statistical confidence when CERVUS was used to infer paternity in a population of red deer (Cervus elaphus). The actual confidence of CERVUS-assigned paternities was not significantly different from that predicted by simulation.

Animals↗

Noninvasive paternity assignment in Gombe chimpanzees.

The relative success of chimpanzee male mating strategies, the role of male dominance rank and the success of inbreeding avoidance behaviour can only be assessed when paternities are known. We report the probable paternities of 14 chimpanzees included in a long-term behavioural study of chimpanzees (Pan troglodytes schweinfurthii) at Gombe National Park, Tanzania. DNA samples were collected noninvasively from shed hair and faeces and genotyped using 13-16 microsatellite loci characterized in humans. All 14 offspring could be assigned to fathers within the community. While there is a positive relationship between male rank and reproductive success, we demonstrate that a range of male mating strategies (possessiveness, opportunistic mating and consortships) can lead to paternity across all male ranks. Several adult females were at risk of breeding with close male relatives. Most successfully avoided close inbreeding but in one case a high-ranking male in the community mated with his mother and produced an offspring. In contrast to recent data on chimpanzees (P. t. verus) from the Taï forest, Côte d'Ivoire, no evidence of extra-group paternity was observed in our study. Reanalysis of Taï data using a likelihood approach casts doubt on the occurrence of extra-group paternity in that community as well.

Animals↗

Down's syndrome and paternal age in Norway.

There is strong evidence for an effect of maternal age on the risk of Down's syndrome. An effect of paternal age has been suspected, but so far neither confirmed nor completely excluded. Large population-based data that allow detailed adjustment for maternal age are needed for a definitive analysis of the paternal age effect. We used data from the Medical Birth Registry of Norway recorded from 1967 to 1998. A total of 1738852 children were included in the analysis. A total of 10.3 per 10000 newborns had Down's syndrome. The data were fitted to logistic regression models with careful control for maternal age, birth calendar year and place of birth. When maternal age was adjusted for using categories of 5-year intervals, residual confounding still resulted in a strong effect of paternal age. However, when the shape of the effect of maternal age was well captured by the model, the estimated effect of paternal age was weak (1.11-fold increased risk per 10 years of paternal age, 95% CI of odds ratio 0.99, 1.22) and not statistically significant.

Adult↗

Analysis of paternity. The use of HLA and red cell antigens.

Over a 6-year period, 866 cases were analyzed for disputed parentage. In 194 cases (22%), the alleged father was excluded as the biological father. One hundred and eight-one cases (93%) were direct exclusions, and 13 cases (7%) were indirect exclusions. Ninety-two percent of falsely accused men were identified by typing for HLA antigens alone. Exclusions based solely on red cell data occurred in 8 percent of the cases. When only HLA testing was performed, 177 of 362 (43%) cases had a probability of paternity of greater than or equal to 95 percent. When both HLA and red cell typings were performed, 110 of 160 (69%) cases had a probability of paternity of greater than or equal to 95 percent. No significant differences in the proportion of exclusions or proportion of alleged fathers with a probability of paternity of greater than or equal to 95 percent were observed between Caucasians or blacks. We conclude that typing for HLA antigens provides the most powerful data for excluding or including an alleged father. However, typing for red cell antigens adds significant data in excluding a falsely accused man and in determining the probability of paternity at a critical level (greater than or equal to 95%). In addition, the current study suggests that additional assays are needed to identify genetic characteristics of cases with probability of paternity less than 95 percent.

Blood Group Antigens↗

An unexcluded paternity case investigated with hypervariable DNA loci.

A paternity case involving a putative father, a child, and the mother was referred to our laboratory for testing. Parentage was not excluded with 23 kinds of standard blood group markers and HLA, but the putative father requested more-affirmative evidence of paternity. Seven kinds of DNA probes that recognize hypervariable loci were applied. On the basis of the allelic frequencies and their confidence intervals previously reported among unrelated Japanese individuals, as well as confirmed codominant segregation of the polymorphism, the exclusion probability and paternity index were calculated for this case. The cumulative paternity index from the seven DNA probes was 1.4 x 10(6), which was 316 times higher than that from the 23 standard blood group markers and HLA. Accordingly, DNA polymorphism is considered to be informative enough for paternity testing.

Blood Grouping and Crossmatching↗