Expected and observed proportion of subjects excluded from paternity by blood phenotypes of a child and its mother in a sample of 171 families

The proportion of exclusion for a given mother-child pair is the proportion of males excluded from the paternity of this child of a known mother and may be calculated given both the child's and mother's phenotypes and the population gene frequencies. Its expected value in the population is equal to the probability of exclusion, which expresses a laboratory's capability to exclude from paternity nonbiological fathers.

In a sample of 171 families examined for 20 genetic systems at the National Blood Group Reference Laboratory, 25 exclusions of putative fathers were detected. The ranking by efficiency of the systems used in these exclusions fits the “expectation of their efficiency,” and the average proportion of males excluded by the child's and mother's phenotypes is not different from the expected proportion. Additionally, the repetition of exclusions in an incompatible putative father-mother-child trio is not dependent on the overall proportion of males excluded by the mother and the child, but rather on some high values of the proportion of excluded men in some specific systems.

Here, formulas and some factors modifying these parameters as well as a more efficient sequence of examinations to exclude paternity than has previously been used are given. Using this sequence, laboratories which carry out several analyses per day can work by levels of five examinations at a time, done in a particular order, to obtain a rather rapid exclusion of certain families.

     

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%.     

Estimation of nonpaternity in the Mexican population of Nuevo Leon: A validation study with blood group markers

A method for estimating the general rate of nonpaternity in a population was validated using phenotype data on seven blood groups (A₁A₂BO, MNSs, Rh, Duffy, Lutheran, Kidd, and P) on 396 mother, child, and legal father trios from Nuevo León, Mexico. In all, 32 legal fathers were excluded as the possible father based on genetic exclusions at one or more loci (combined average exclusion probability of 0.694 for specific mother-child phenotype pairs). The maximum likelihood estimate of the general nonpaternity rate in the population was 0.118 ± 0.020. The nonpaternity rates in Nuevo León were also seen to be inversely related with the socioeconomic status of the families, i.e., the highest in the low and the lowest in the high socioeconomic class. We further argue that with the moderately low (69.4%) power of exclusion for these seven blood group systems, the traditional critical values of paternity index (PI ≥ 19) were not good indicators of true paternity, since a considerable fraction (307/364) of nonexcluded legal fathers had a paternity index below 19 based on the seven markers. Implications of these results in the context of genetic-epidemiological studies as well as for detection of true fathers for child-support adjudications are discussed, implying the need to employ a battery of genetic markers (possibly DNA-based tests) that yield a higher power of exclusion. We conclude that even though DNA markers are more informative, the probabilistic approach developed here would still be needed to estimate the true rate of nonpaternity in a population or to evaluate the precision of detecting true fathers. Am J Phys Anthropol 109:281–293, 1999. © 1999 Wiley-Liss, Inc.     

Calculation of the proportion of men excluded from paternity by HLA typing of the mother and child

When filiation research shows that paternity is possible, French legislation recommends the calculation of two coefficients: 1. paternity probability (CP); 2. percentage of random men excluded from paternity by genetic markers of the mother and the child (PEme). A method is proposed, allowing the determination of PEme for the HLA system and PEme for the various systems employed. The calculations, relatively simple, can be worked out quickly and without risk of error, using a computer. We successively look at simple cases, complex cases and unusual cases: maternal death, consanguinity problems, racial problems. HLA-A, B, C, DR, DQ typing almost always leads to the exclusion of more than 98% of innocent men (PEme greater than 0.98). The HLA system clearly appears to be the most conclusive of the systems utilized by experts.     

Characterization of eight VNTR loci by agarose gel electrophoresis

Allelic frequencies and their confidence intervals were obtained for eight independent VNTR loci from a sample of more than 75 Utah Caucasians. Using high-resolution agarose gel electrophoresis, we were able to resolve alleles at the D17S5 locus that differed by only one repeating unit; it was therefore possible to name the alleles according to the number of repeating units each contained. Two a priori probabilities were calculated for each VNTR locus separately and for all eight loci jointly: (i) the "power of exclusion" for an alleged father/mother/child trio and for an alleged parent/child duo, and (ii) the "probability of matching" when two unrelated individuals or two siblings are genotyped.     

False paternity exclusion in the Rh system: use of cytofluorometry analysis

In a two-men paternity testing analysis, the first putative father was definitely excluded by six blood group systems; the second one was apparently excluded in the Rh system. In fact, an analysis by flow-cytometry demonstrated that this false exclusion was due to the presence of a D--haplotype in the father and child.     

Characterization of a spontaneous mutation to a beta-thalassemia allele.

We have studied a nuclear family containing a single child with severe beta-thalassemia intermedia, a Greek-Cypriot mother with hematological findings of beta-thalassemia trait, and a Polish father who is hematologically normal. Since both the child and her father were heterozygous for a DNA polymorphism within the beta-globin gene, it was possible to clone and sequence the beta-globin gene identical by descent from both the child and her father. A nonsense mutation in codon 121 (GAA----TAA) was found in the beta-globin gene of the child, while the same gene from her father lacked this mutation and was normal. This mutation has not been previously observed among over 200 beta-thalassemia genes characterized in Caucasians. Since the mutation eliminates an EcoRI site in the beta-globin gene, we could show that the mutation is not present in genomic DNA of the father. To rule out germinal mosaicism, sperm DNA of the father was also digested with EcoRI, and the mutant EcoRI fragment was not observed under conditions that would detect the mutation if it were present in at least 2% of sperm cells. Routine HLA and blood group testing supported stated paternity. In addition, studies with 17 DNA probes that detect multiple allele polymorphisms increased the probability of stated paternity to at least 10(8):1. These data provide evidence that the G----T change in codon 121 of the beta-globin gene in the child is the result of a spontaneous mutation that occurred during spermatogenesis in a paternal germ cell.     

Exclusion probabilities for pedigree testing farm animals

Pedigree testing, using genetic markers, may be undertaken for a variety of situations, of which the classical paternity testing is only one. This has not always been made clear in the literature. Exclusion probabilities associated with various testing situations, including the use of autosomal or X-linked codominant marker systems with any number of alleles, are presented. These formulae can be used to determine the appropriate exclusion probability for the situation being investigated. One such situation is where sire groups of progeny are to be verified without knowledge of the dams' genotypes, in which case the classical paternity exclusion probability is too high, and if used may result in an optimistic declaration about the progeny that have not been excluded. On the other hand, if mating pairs are known then incorrect progeny can be excluded at a higher rate than suggested by paternity exclusion calculations. The formulae also assist in determining the usefulness of X-linked markers, particularly if the pedigree checks involve progeny of only one sex. A system of notation that is useful for the algebraic manipulation of genetic probabilities, including exclusion probabilities as presented here, is also given.     

Exclusion probabilities for single-locus paternity analysis when related males compete for matings

The statistical power of single-locus paternity analyses has previously been assessed by calculating an expected exclusion probability ( E ), the probability of excluding a randomly chosen nonfather. This E -statistic assumes that putative sires are a random selection of individuals from a panmictic study population. In species that display male natal philopatry, closely related individuals may be the principal competitors for paternity. In such structured populations, the E statistic will overestimate exclusion probability because males competing for paternity are more closely related than males chosen randomly from the population. A suite of loci thought to be sufficient for a panmictic population may frequently incorrectly assign paternity to close relatives of true sires. This study provides equations for calculating the expected probability of excluding a close male relative of the genetic sire ( Erel ) for any genotyping system that uses codominant markers. We also describe the use of Monte Carlo modelling to estimate exclusion probabilities when multiple male relatives compete for paternity. We show that the utility of a set of codominant markers will depend on the breeding behaviour and social system of the species in question.     

LOD Score Exclusion Analyses for Candidate QTLs using Random Population Samples

While extensive analyses have been conducted to test for, no formal analyses have been conducted to test against, the importance of candidate genes as putative QTLs using random population samples. Previously, we developed an LOD score exclusion mapping approach for candidate genes for complex diseases. Here, we extend this LOD score approach for exclusion analyses of candidate genes for quantitative traits. Under this approach, specific genetic effects (as reflected by heritability) and inheritance models at candidate QTLs can be analyzed and if an LOD score is < or = -2.0, the locus can be excluded from having a heritability larger than that specified. Simulations show that this approach has high power to exclude a candidate gene from having moderate genetic effects if it is not a QTL and is robust to population admixture. Our exclusion analysis complements association analysis for candidate genes as putative QTLs in random population samples. The approach is applied to test the importance of Vitamin D receptor (VDR) gene as a potential QTL underlying the variation of bone mass, an important determinant of osteoporosis.     

The relevance of paternity analysis in Romanian population using the D1S80 locus

At present, DNA fingerprinting for human identification and paternity testing is a necessary and usual procedure. D1S80 is one of the best known polymorphic loci showing a VNTR, and exhibiting a high heterozygosity. This genetic locus, with a Tsp 509 I polymorphism of its 5' flanking sequence (1, 9), have been successfully amplified from human genomic DNA isolated from blood. The Tsp 509 I polymorphism was detected by restriction after PCR amplification. We tested the relevance of paternity analysis using the D1S80 locus considering the allele frequency distribution characteristic for our country. Paternal and maternal bands were compared with the children's DNA patterns. Our data include a comparison between D1S80 alleles amplified from mother, child and the supposed father for three tested families. This study was the first of this type made in Romania. We concluded a good power of discrimination and exclusion for this locus. It can be used successfully in the case of subtypes with low frequencies, and this is frequent for our population because of the high heterozygosity of D1S80 subtypes in Romanian population. We recommend the D1S80 use for exclusion paternity tests in Romanian population, as a very useful molecular tool, but we also recommend a complete set of molecular markers for confirmation paternity test in the same population.     

A de novo recombination in the ABO blood group gene and evidence for the occurrence of recombination products

We have encountered a paternity case where exclusion of the putative father was only observed in the ABO blood group (mother, B; child, A1; putative father, O), among the many polymorphic markers tested, including DNA fingerprints and microsatellite markers. Cloning a part of the ABO gene, PCR-amplified from the trio’s genomes, followed by sequencing the cloned fragments, showed that one allele of the child had a hybrid nature, comprising exon 6 of the B allele and exon 7 of the O1 allele. Based on the evidence that exon 7 is crucial for the sugar-nucleotide specificity of A1 and B transferases and that the O1 allele is only specified by the 261G deletion in exon 6 of the consensus sequence of the A1 allele, we concluded that the hybrid allele encodes a transferase with A1 specificity, resulting, presumably, from de novo recombination between the B and O1 alleles of the mother during meiosis. Screening of random populations demonstrated the occurrence of four other hybrid alleles. Sequencing of intron VI from the five hybrid alleles showed that the junctions of the hybrid alleles were located within intron VI, the intron VI-exon 7 boundaries, or exon 7. Recombinational events seem to be partly involved in the genesis of sequence diversities of the ABO gene. Received: 25 October 1996     

Beobachtung eines Faktorenaustausches zwischen den Blutgruppen-Genorten MN und Ss

In a family, in the first instance investigated in a linkage study, blood grouping showed MNSs distributions which could not be expected by inheritance of complexes MS, Ms, NS, and Ns, as generally assumed. (father: MS/Ns, mother: MS/Ns or Ms/NS, first child: MS/NS, second child: Ns/Ns). Since illegitimacy of one or both of the children could be excluded practically with certainty, only a mutation at the MN or Ss locus, or a crossing-over between the MN and the Ss locus can explain the children's genotypes, the crossing-over being the most probably right interpretation of MNSs findings in this family.

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Mit Unterstützung durch die Deutsche Forschungsgemeinschaft.     

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.     

A Gc silent allele encountered in a paternity case

A father-child incompatibility only in the Gc system was detected in a paternity case tested at our laboratory. Quantitative determination revealed that the Gc level in the two individuals was less than 50% of the normal mean value. Evaluation of the probability calculation for the putative father using all other markers showed that he was the biological father with a very high probability. Thus it was concluded that a silent allele Gc*QO was transmitted from the father to the child.     

Complexities in Research on Fathering: Illustrations from the Tufts Study of Young Fathers

Theory and research suggest that the transition to parenthood is a major life transition, and that adaptation to the parenting role is influenced by a complex set of factors, including the relationship with the child's mother, family of origin, and how the father is situated within sociocultural contexts. The father–]mother relationship is particularly important for men making the transition to fatherhood. This study examined patterns of fathering among young fathers (15–24 years) and investigated how fathers' relationships with the mothers of their young children (infants and toddlers) were related to fathering. In general, higher quality father–mother relationships were related to greater father involvement with children; when mothers were perceived as barriers to involved fathering fathers also had less accurate and adaptive parenting knowledge, attitudes, and behavior. Person-centered analyses revealed quite complex relations between father–mother relationships and father–child interaction. One pattern showed strong positive father–mother relationships associated with a disengaged pattern of father–child interaction, while another pattern showed sensitive and positive father–child engagement in the context of negative or distant father–mother relationships. Four patterns of association between fathering and mother–father relationships were demonstrated. Results highlight the complexity of understanding fathering and family relationships among young fathers.     

应用微卫星分型方法进行大熊猫父亲鉴定

1979年我们利用水稻花粉单倍体植株的 茎节、幼穗、叶鞘和叶片等组织进行离体培养, 诱导出二倍体植株。     

New mutation versus exclusion at the alpha-1-antitrypsin locus: a multifaceted approach in a problematical paternity case

In a case of disputed paternity with overwhelming indications of fatherhood for the putative father, as supported by serological tests and biostatistical evaluation, a classical exclusion constellation was found at the alpha 1-antitrypsin (PI) locus: mother PI M1; child PI M1M3, and putative father PI M1M2. Additional studies included PI oligonucleotide phenotyping and DNA fingerprint analysis. Results from the entire data set led us to assume a rare genetic event at the paternal PI locus. Intracistronal crossing-over offered the most parsimonious explanation, and was compatible with the PI gene DNA sequence and the amino acid sequences of the molecule and its allelic forms, as well as with the experimental findings.     

Effectiveness of 10 polymorphic microsatellite markers for parentage and pedigree analysis in plateau pika (Ochotona curzoniae)

Background

The plateau pika (Ochotona curzoniae) is an underground-dwelling mammal, native to the Tibetan plateau of China. A set of 10 polymorphic microsatellite loci has been developed earlier. Its reliability for parentage assignment has been tested in a plateau pika population. Two family groups with a known pedigree were used to validate the power of this set of markers.

Results

The error in parentage assignment using a combination of these 10 loci was very low as indicated by their power of discrimination (0.803 - 0.932), power of exclusion (0.351 - 0.887), and an effectiveness of the combined probability of exclusion in parentage assignment of 99.999%.

Conclusion

All the offspring of a family could be assigned to their biological mother; and their father or relatives could also be identified. This set of markers therefore provides a powerful and efficient tool for parentage assignment and other population analyses in the plateau pika.     

Distinguished words in data sequences: Analysis and applications to neural coding and other fields

This paper concerns sequences of letters in which certain “distinguished” words are of interest. Such sequences arise as data in numerous fields including genetics and neuroscience. A probability distribution is given for the number of occurrences of a chosen word in a randomized sequence of letters. Such words are considered “favored” if they occur more than expected at random. Favored words have been discovered in nerve impulse trains and may reflect a neural coding scheme. This article is dedicated to my mother, Margaret Oakley Dayhoff, whose enthusiasm encouraged me to pursue research in mathematical biology.