Probability of paternity exclusion when relatives are involved.

In diagnosis of paternity by means of polymorphic markers, the proportion of men excluded on the basis of the phenotypes of the mother and child is the best index for controlling information. Its expected value, the probability of exclusion of a male chosen at random with respect to a random child-mother couple, calculated from gene frequencies of every genetic system, may be modified by a close relationship between the mother, the real father, and the presumptive father. The father and even more the brother of the mother, if he is the father of the child, diminishes the probability of exclusion of an individual chosen at random in the population, and if he is falsely accused, he has a higher probability of being excluded. On the other hand, the brother of the real father chosen at random in the population has the least chance of being excluded. The two different rules of exclusion are involved in the calculations, the first one being the more reliable.     

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 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%.     

Rapid and efficient resolution of parentage by amplification of short tandem repeats.

Short tandem repeat (STR) loci are highly informative polymorphic loci that are gaining popularity for identity testing. We have conducted parentage testing by using nine STR loci on 50 paternity trios that had been previously tested using VNTR loci. These nine unlinked STR loci are amplified in three multiplex reactions and, when examined for genetic informativeness, provide a combined average power of exclusion of 99.73% (Caucasian data). The informative value of the selected loci is based on extensive STR typing of four racial/ethnic populations. In 37 of the 50 cases, paternity could not be excluded by any of the loci. In the remaining 13 cases, paternity was excluded by at least two of the STR markers. The probability of paternity calculated for the alleged father of each matching trio was > 99% in 36 of the 37 inclusion cases. All data agreed with the results reported using VNTR loci and conventional Southern technology. Our studies validate the use of DNA typing with STR loci for parentage testing, thus providing an accurate, highly sensitive, and rapid assay.     

Non-invasive giant panda paternity exclusion

Giant panda hair samples obtained by noninvasive methods served as a source of DNA for amplification of seven giant panda microsatellite loci utilizing the polymerase chain reaction. Thirteen giant pandas held in Chinese zoos were tested for identification of paternity. Some males listed as sires have been excluded as the biological father of captive-born giant pandas. Because of the death of some potential sires, paternity is still not assigned for some giant pandas, although there is a high likelihood that paternity assignment could be made if postmortem samples are available for genetic analysis. The DNA microsatellite variation assayed by the test we have developed provides a rapid, highly informative, and noninvasive method for paternity identification in giant pandas. © 1994 Wiley-Liss, Inc.     

The Null Relation between Father Absence and Earlier Menarche

Researchers have claimed that the absence of a biological father accelerates the daughter’s menarche. This claim was assessed by employing a large and nationally representative sample of Indonesian women. We analyzed 11,138 ever-married women aged 15+ in the Indonesian Family Life Survey 2015. We regressed age at menarche on the interaction of father absence (vs. presence) and mother absence (vs. presence) at age 12 with or without childhood covariates. For robustness checks, we performed a power analysis, re-ran the same specification for various subgroups, and varied the independent variable of interest. All results produced a null relation between father absence and age at menarche. The power analysis suggests that a false negative was unlikely. Our review of the literature indicates that the claim of the relation between father absence and earlier menarche was based on weak statistical foundations. Other studies with higher-quality datasets tended to find no relation, and our results replicated this tendency. Therefore, the influence of father absence does not appear to be universal.     

Impact of a chromosome X STR Decaplex in deficiency paternity cases

Deficiency paternity cases, characterized by the absence of the alleged father, are a challenge for forensic genetics. Here we present four cases with a female child and a deceased alleged father in which the analysis of a set of 21 or 22 autosomal STRs (AS STRs) produced results within a range of doubt when genotyping relatives of the alleged father. Aiming to increase the Paternity Index (PI) and obtain more reliable results, a set of 10 X-linked STR markers, developed by the Spanish and Portuguese Group of the International Society for Forensic Genetics (ISFG), was then added. Statistical analysis substantially shifted the results towards the alleged fatherhood in all four cases, with more dramatic changes when the supposed half-sister and respective mother were the relatives tested.     

Paternity discrimination and inter-group relationships of chimpanzees at Bossou

A small group of wild chimpanzees at Bossou, southeastern Guinea, is semi-isolated, occupying a home-range which is several kilometers from those of other groups. The group has had only one adult male since 1985, raising the probability of inbreeding. Direct observation suggests that this male was the father of all infants born in the group since 1985. In 1991 individually identified samples of food wadges, hair, and feces were collected from most of the group members. These samples were analyzed using GT dinucleotide repeat polymorphisms to determine familial relationships. The genetic analysis revealed that the resident adult male was the probable father of only three out of the four infants analyzed. It is suspected that an adult male from a neighboring group was the father of the fourth infant, born in late 1986 or early 1987.     

Segregation analysis of rare autosomal fragile sites

Summary Segregation analyses were performed on pedigrees with rare autosomal fragile sites. The results of the analysis of pedigrees with folate sensitive fragile sites, including 2q1, 6p23, 7p11, 8q22, 9q32, 10q23, 11q13, 11q23, 12q13, 16p12, and 20p11, suggested that expression of the gene depended on the carrier parent: it was only 50% penetrant when transmitted by a carrier father, but fully penetrant when transmitted by a carrier mother. Pedigrees with the bromodeoxyuridine (BrdU) fragile site, fra(10)(q25), showed the same trend but the results were not statistically significant. In addition, 38 of the 44 probands with folate sensitive or BrdU-sensitive fragile sites received the gene from their carrier mother and only six received it from their father. In contrast, the analysis of pedigrees with the distamycin A-inducible site, fra(16)(q22), gave the results expected for a simple codominant trait with complete penetrance. Probands with this fragile site received the gene equally from mothers or fathers. The genetic implications of these results are discussed.     

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.     

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.     

Molecular definition of the 11p15.5 region involved in Beckwith-Wiedemann syndrome and probably in predisposition to adrenocortical carcinoma

Summary To define more precisely, in molecular terms, the region involved in Beckwith-Wiedemann syndrome (BWS), we have studied patients with BWS and a constitutional duplication of 11p15 using eight 11p15 markers. In the first case with a de novo duplication and extra material on 11p, the region spanning pter to CALCA, excluded, was duplicated. In the second case, the rearrangement was characterized using somatic cell hybrids established with lymphocytes from the father who carried a balanced translocation t(11;18)(p15.4;p11.1). The breakpoint lay exactly in the same region. It could thus be inferred that the two sons, who were the first cases reported of BWS with dup11p15 and adrenocortical carcinoma (ADCC), carried a duplication similar to that observed in the first case. Together with evidence for specific somatic chromosomal events leading to loss of 11p15 alleles in familial cases of ADCC, it can be hypothesized that a gene involved in predisposition to ADCC maps to region 11p15.5.     

FMR1 gene deletion/reversion: a pitfall of fragile X carrier testing

The Fragile X syndrome is, in the majority of cases, caused by CGG trinucleotide amplification within the FMR1 gene. The syndrome is rarely caused by point mutations or deletions. Here we describe a family with 2 sons and 1 daughter affected by Fragile X syndrome and 2 unaffected daughters whose carrier status was unknown prior to this study. Analysis of DNA from each of the 2 daughters revealed two alleles in the normal size range. However, 1 daughter carried one allele of 10 CGG repeats that was not present in either the mother or the father. No evidence for mosaicism could be detected. Haplotype analysis of flanking polymorphic markers revealed that the 10 CGG allele was derived from the mutated allele inherited from the mother. Thus, this case most likely represents an additional case of a reverse mutation from a premutation allele in a female to a normal-sized allele in the offspring. It remains unclear how frequently such reversion events occur. The observation has important consequences for genetic testing, because many laboratories prescreen for the Fragile X syndrome by determining the length of the CGG repeat using PCR. If this shows alleles in the normal size range, a diagnosis of Fragile X syndrome is considered to be excluded. Because the routine PCR and/or Southern blot analyses alone may yield false-negative results in cases of a regression of the number of CGG repeats, we strongly recommend the inclusion of fragment length or haplotype analysis when determining the carrier status within Fragile X syndrome families.     

Presence of the father and parental experience have differentiated effects on pup development in Mongolian gerbils (Meriones unguiculatus)

Conflicting data exist on the importance of the father and parental experience during development in rodents. The purpose of this study was to investigate the effects of these two variables on development in Mongolian gerbils. Forty pairs of males and females with a litter size of between 4 and 7 pups were used as subjects. Twenty couples had no experience in raising young. After the birth of their pups, four experimental groups were formed: (I) inexperienced mother and father; (II) inexperienced mother; (III) experienced mother and father and (IV) experienced mother. When the pups reached 10 days of age, pup and parental behavior was recorded in experimental sessions of 15 min on 11 consecutive days. Through the statistical analysis it was found that the presence of the father significantly increased the physical contact between pups and parents and that pups opened their eyes earlier in comparison to the groups without the father. On the other hand, parental experience had a significant influence on the behavior of the pups (locomotion inside and outside the nest, and self-grooming). The results of this study suggest that parental experience and the presence of the father have differentiated effects on development in Mongolian gerbils.     

Paternity assessment in wild groups of toque macaques Macaca sinica at Polonnaruwa, Sri Lanka using molecular markers

Genetic variation at four microsatellite loci in conjunction with that at a highly variable allozyme locus was used to analyse paternity over a 12-year period in 13 social groups of toque macaques Macaca sinica inhabiting a natural forest in Polonnaruwa, Sri Lanka. Paternity exclusion analysis revealed that the set of offspring produced by a female usually consists of half-siblings because few males father more than one offspring with a particular female. No evidence of offspring produced by matings between first degree relatives was found. The social unit in toque macaques was not identical to the reproductive unit and the possibility of paternity by males outside the social group should be considered when estimating male reproductive output. Although it was common for multiple males to father offspring in a social group each year, reproduction within a group during a breeding season tended to be limited to a few males. The mean number of males reproducing per group per year was independent of the number of males in a group. The paternity data suggests that many males may father relatively few offspring during their entire lives and that the effective population size for toque macaques may be much smaller than indicated by demographic data.     

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.     

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.     

Tracking microdeletions of the AZF region in a patrilineal line of infertile men

Male infertility is considered to be a difficult-to-treat condition because it is not a single entity, but rather reflects a variety of different pathologic conditions, thus making it difficult to use a single treatment strategy. Structural alterations in the Y chromosome have been the principal factor responsible for male infertility. We examined 26 family members of 13 patients with male infertility who showed deletions in the AZF region. In family 1, the father and a brother did not show microdeletions. However, a son showed a microdeletion in AZFa (sY84) and an azoospermic sperm analysis, but another son had a microdeletion in AZFa (sY84) and AZFb (sY127) and a normal sperm analysis. The father of family 2, with severe oligozoospermia, had a microdeletion in the AZFa region (sY84) and his son, conceived by intracytoplasmic sperm injection, also showed the same microdeletion. In the other families, only the men with an altered sperm analysis had a microdeletion. It is possible that in family 1, the father and brother who did not show microdeletions in this study, could have microdeletions in regions upstream or downstream of the one analyzed. The treatment with intracytoplasmic sperm injection can result in vertical transmission of microdeletions of the AZF region and can also cause the expansion of a de novo mutation. This finding reinforces the necessity of an investigation of microdeletions of the Y chromosome in individuals who are candidates for assisted reproduction, as well as genetic counciling and follow-up.     

Patau综合征患者额外13号染色体父亲起源

报告1例孕38周经剖腹产出生的畸形男儿。患儿双侧唇裂,严重腭裂,胸骨畸形,骶部脊柱裂,双侧睾丸未降,足内翻。出生后10分钟由于呼吸衰竭而夭折。患儿经外周血淋巴细胞染色体核型分析为47,XY,+13,后经荧光原位杂交技术加以证实。对患儿及其父母进行短重复序列D13S317位点检测,证实患儿额外的13号染色体源自父亲第一次减数分裂不分离。     

Complete paternal uniparental isodisomy for chromosome 1 revealed by mutation analyses of the<Emphasis Type="Italic"> TRKA (NTRK1)</Emphasis> gene encoding a receptor tyrosine kinase for nerve growth factor in a patient with congenital insensitivity to pain with anhidrosis

Uniparental disomy (UPD) is defined as the presence of a chromosome pair that derives from only one parent in a diploid individual. The human TRKA gene on chromosome 1q21-q22 encodes a receptor tyrosine kinase for nerve growth factor and is responsible for an autosomal recessive genetic disorder: congenital insensitivity to pain with anhidrosis (CIPA). We report here the second case of paternal UPD for chromosome 1 in a male patient with CIPA who developed normally at term and did not show overt dysmorphisms or malformations. He had only the usual features of CIPA with a homozygous mutation at the TRKA locus and a normal karyotype with no visible deletions or evidence of monosomy 1. Haplotype analysis of the TRKA locus and allelotype analyses of whole chromosome 1 revealed that the chromosome pair was exclusively derived from his father. Non-maternity was excluded by analyses of autosomes other than chromosome 1. Thus, we have identified a complete paternal isodisomy for chromosome 1 as the cause of reduction to homozygosity of the TRKA gene mutation, leading to CIPA. Our findings further support the idea that there are no paternally imprinted genes on chromosome 1 with a major effect on phenotype. UPD must be considered as a rare but possible cause of autosomal recessive disorders when conducting genetic testing.