Trim66's paternal deficiency causes intrauterine overgrowth.

The tripartite motif-containing protein 66 (TRIM66, also known as TIF1-delta) is a PHD-Bromo-containing protein primarily expressed in post-meiotic male germ cells known as spermatids. Biophysical assays showed that the TRIM66 PHD-Bromodomain binds to H3 N-terminus only when lysine 4 is unmethylated. We addressed TRIM66's role in reproduction by loss-of-function genetics in the mouse. Males homozygous for Trim66-null mutations produced functional spermatozoa. Round spermatids lacking TRIM66 up-regulated a network of genes involved in histone acetylation and H3K4 methylation. Profiling of H3K4me3 patterns in the sperm produced by the Trim66-null mutant showed minor alterations below statistical significance. Unexpectedly, Trim66-null males, but not females, sired pups overweight at birth, hence revealing that Trim66 mutations cause a paternal effect phenotype.

Paternally Inherited Noonan Syndrome Caused by a PTPN11 Variant May Exhibit Mild Symptoms: A Case Report and Literature Review.

BACKGROUND: Noonan syndrome (NS)/Noonan syndrome with multiple lentigines (NSML) is commonly characterized by distinct facial features, a short stature, cardiac problems, and a developmental delay of variable degrees. However, as many as 50% of individuals diagnosed with NS/NSML have a mildly affected parent or relative due to variable expressivity and possibly incomplete penetrance of the disorder, and those who are recognized to have NS only after a diagnosis are established in a more obviously affected index case. METHODS: In order to collect intergenerational data reported from previous studies, electronic journal databases containing information on the molecular genetics of PTPN11 were searched from 2000 to 2022. RESULTS: We present a case of a proband with a PTPN11 variant (c.1492C > T/p.Arg498Trp) inherited from an asymptomatic father, displaying only mild intellectual disability without classical symptoms of NS. Among our cases and the reported NS cases caused by the PTPN11 p.Arg498Trp variant, cardiac abnormalities (6/11), facial dysmorphism (7/11), skin pigmentation (4/11), growth problems (4/11), and sensorineural hearing loss (2/11) have been observed. NS/NSML patients with the PTPN11 p.Arg498Trp variant tend to exhibit relatively lower frequencies of skin pigmentation, facial dysmorphism and cardiac abnormalities and mild symptoms compared to those carrying any other mutated PTPN11. CONCLUSIONS: Paternally inherited NS/NSML caused by a PTPN11 p.Arg498Trp variant, including our cases, may exhibit relatively lower frequencies of abnormal features and mild symptoms. This could be ascribed to potential gene-gene interactions, gene-environment interactions, the gender and phenotype of the transmitting parent, or ethnic differences that influence the clinical phenotype.

Relationship between paternal factors and embryonic aneuploidy of paternal origin.

OBJECTIVE: To determine if there is a relationship between paternal factors and embryonic aneuploidy of paternal origin using preimplantation genetic testing for aneuploidy (PGT-A). DESIGN: Retrospective cohort. SETTING: Academic. PARTICIPANTS: Couples undergoing in vitro fertilization with PGT-A. INTERVENTIONS: None. MAIN OUTCOME MEASURE: To determine if there is an association between paternal age, body mass index (BMI), or semen analysis parameters and paternal aneuploidy. RESULTS: From January 2015-2020, 453 in vitro fertilization cycles (1,720 embryos) underwent PGT-A using single nucleotide polymorphism microarrays with parental support bioinformatics. The mean (±SD) was 36.5 (±3.5) years for maternal age, 39.5 (±5.5) years for paternal age, 24.7 (±5.0) kg/m2 for maternal BMI, and 27.6 (±4.3) kg/m2 for paternal BMI. Embryonic aneuploidy of paternal origin was found in 8.4% (144/1,720) embryos. There were 1,533 embryos with a recorded paternal BMI. Rates of embryonic aneuploidy of paternal origin were similar between men across BMI groups: BMI 18-24.9 kg/m2 was 7.2% (referent); BMI 25-29.9 kg/m2 was 8.4% (odds ratio [OR], 1.12; 95% confidence interval [CI], 0.79-1.82); and BMI ≥30 kg/m2 was 9.1% (OR, 1.31; 95% CI, 0.83-2.08). There were 854 embryos from men with a normal and 866 from men with an abnormal semen analysis. No differences were found in the rate of embryonic aneuploidy of paternal origin between men with normal and abnormal sperm concentration, total count, motility, progressive motility, or morphology. No significant difference was seen in rates of aneuploidy between men aged <50 years and those aged ≥50 years (OR, 1.69; 95% CI, 0.96-2.98). CONCLUSION: No association was found between paternal age, BMI, or semen analysis parameters and paternal aneuploidy.

Sex differences in MEN 2A penetrance and expression according to parental inheritance.

OBJECTIVE: This study aimed to delineate the age-dependent clinical penetrance and expression of heterozygous rearranged during transfection (RET) missense mutations associated with multiple endocrine neoplasia 2A (MEN2A) according to parental inheritance. DESIGN: This was an observational study of RET carriers operated for MEN2A-associated tumors between 1985 and 2021. METHODS: Kaplan-Meier time-to-event and multivariable Cox proportional hazards regression analyses were performed on node metastases from medullary thyroid cancer, pheochromocytoma, bilateral pheochromocytoma, and primary hyperparathyroidism. RESULTS: Some 405 (70.1%) of 578 patients carrying heterozygous MEN2A RET missense mutations had information about the parental inheritance of the trait. On Kaplan-Meier analysis, offspring who inherited the trait from the father developed node metastases (Plog-rank= 0.007), pheochromocytoma (Plog-rank= 0.029), bilateral pheochromocytoma (Plog-rank= 0.002), and primary hyperparathyroidism (Plog-rank= 0.018) at a significantly younger age than offspring who inherited the trait from the mother. On multivariable Cox regression, controlling for index status, offspring sex, and (where feasible) mutational risk, parental inheritance was consistently associated with each MEN2A-associated tumor (hazard ratios (HR) = 1.7-1.8 for the earlier manifestations node metastases and pheochromocytoma vs HR of 2.9-3.4 for the late manifestations bilateral pheochromocytoma and primary hyperparathyroidism). Herein, node metastases were 3.1- and 1.7-fold more closely associated with mutational risk (HR of 5.3 for high and 2.9 for moderate-high risk mutations vs low-moderate risk mutations) than parental inheritance (HR = 1.7). CONCLUSION: These findings illustrate the importance of considering not just mutational risk but also parental inheritance when it comes to personalization of screening for and early detection of the various components of MEN2A-associated tumors.

Ancient DNA at the edge of the world: Continental immigration and the persistence of Neolithic male lineages in Bronze Age Orkney.

Orkney was a major cultural center during the Neolithic, 3800 to 2500 BC. Farming flourished, permanent stone settlements and chambered tombs were constructed, and long-range contacts were sustained. From ∼3200 BC, the number, density, and extravagance of settlements increased, and new ceremonial monuments and ceramic styles, possibly originating in Orkney, spread across Britain and Ireland. By ∼2800 BC, this phenomenon was waning, although Neolithic traditions persisted to at least 2500 BC. Unlike elsewhere in Britain, there is little material evidence to suggest a Beaker presence, suggesting that Orkney may have developed along an insular trajectory during the second millennium BC. We tested this by comparing new genomic evidence from 22 Bronze Age and 3 Iron Age burials in northwest Orkney with Neolithic burials from across the archipelago. We identified signals of inward migration on a scale unsuspected from the archaeological record: As elsewhere in Bronze Age Britain, much of the population displayed significant genome-wide ancestry deriving ultimately from the Pontic-Caspian Steppe. However, uniquely in northern and central Europe, most of the male lineages were inherited from the local Neolithic. This suggests that some male descendants of Neolithic Orkney may have remained distinct well into the Bronze Age, although there are signs that this had dwindled by the Iron Age. Furthermore, although the majority of mitochondrial DNA lineages evidently arrived afresh with the Bronze Age, we also find evidence for continuity in the female line of descent from Mesolithic Britain into the Bronze Age and even to the present day.

The Transgenerational Transmission of the Paternal Type 2 Diabetes-Induced Subfertility Phenotype.

Diabetes is a chronic metabolic disorder characterized by hyperglycemia and associated with many health complications due to the long-term damage and dysfunction of various organs. A consequential complication of diabetes in men is reproductive dysfunction, reduced fertility, and poor reproductive outcomes. However, the molecular mechanisms responsible for diabetic environment-induced sperm damage and overall decreased reproductive outcomes are not fully established. We evaluated the effects of type 2 diabetes exposure on the reproductive system and the reproductive outcomes of males and their male offspring, using a mouse model. We demonstrate that paternal exposure to type 2 diabetes mediates intergenerational and transgenerational effects on the reproductive health of the offspring, especially on sperm quality, and on metabolic characteristics. Given the transgenerational impairment of reproductive and metabolic parameters through two generations, these changes likely take the form of inherited epigenetic marks through the germline. Our results emphasize the importance of improving metabolic health not only in women of reproductive age, but also in potential fathers, in order to reduce the negative impacts of diabetes on subsequent generations.

Evaluating the Impact of Sex-Biased Genetic Admixture in the Americas through the Analysis of Haplotype Data.

A general imbalance in the proportion of disembarked males and females in the Americas has been documented during the Trans-Atlantic Slave Trade and the Colonial Era and, although less prominent, more recently. This imbalance may have left a signature on the genomes of modern-day populations characterised by high levels of admixture. The analysis of the uniparental systems and the evaluation of continental proportion ratio of autosomal and X chromosomes revealed a general sex imbalance towards males for European and females for African and Indigenous American ancestries. However, the consistency and degree of this imbalance are variable, suggesting that other factors, such as cultural and social practices, may have played a role in shaping it. Moreover, very few investigations have evaluated the sex imbalance using haplotype data, containing more critical information than genotypes. Here, we analysed genome-wide data for more than 5000 admixed American individuals to assess the presence, direction and magnitude of sex-biased admixture in the Americas. For this purpose, we applied two haplotype-based approaches, ELAI and NNLS, and we compared them with a genotype-based method, ADMIXTURE. In doing so, besides a general agreement between methods, we unravelled that the post-colonial admixture dynamics show higher complexity than previously described.

Mechanisms of transgenerational immune priming in insects.

Parents invest in their offspring by preparing them for defense against pathogens and parasites that only the parents have encountered, a phenomenon known as transgenerational immune priming (TGIP). The priming effect can be passed maternally or paternally to the next generation, thus increasing the survival of offspring exposed to the same pathogen. The scope of the resulting immune response can be narrow (primarily targeting the triggering pathogen) or much more general, depending on the underlying mechanism. Maternal TGIP is often narrowly focused because the major mechanism is the transfer of microbes or fragments thereof, encountered by mothers at the larval stage, to the developing eggs along with the uptake of lipophorins and vitellogenins. This induces the expression of zygotic defense genes, including those encoding antimicrobial peptides (AMPs), comparable to the defenses observed in the larvae and adults. Maternal TGIP does not appear to involve the direct vertical transmission of immunity-related effectors such as AMPs (or the corresponding mRNAs) to the eggs. Parental investment in offspring is also mediated by epigenetic mechanisms such as DNA methylation, histone acetylation and microRNA expression, which can be imprinted on the gametes by either parent without changes in the DNA sequence. Epigenetic inheritance is the only known mechanism of paternal TGIP, and results in a more general fortification of the immune response. This review considers the mechanistic basis of TGIP, its role in evolutionary processes such as the establishment of resistance against pathogens, and the impact of pathogens and parasites on the epigenetic machinery of host insects.

Sequencing an F1 hybrid of Silurus asotus and S. meridionalis enabled the assembly of high-quality parental genomes.

Genome complexity such as heterozygosity may heavily influence its de novo assembly. Sequencing somatic cells of the F1 hybrids harboring two sets of genetic materials from both of the paternal and maternal species may avoid alleles discrimination during assembly. However, the feasibility of this strategy needs further assessments. We sequenced and assembled the genome of an F1 hybrid between Silurus asotus and S. meridionalis using the SequelII platform and Hi-C scaffolding technologies. More than 300 Gb raw data were generated, and the final assembly obtained 2344 scaffolds composed of 3017 contigs. The N50 length of scaffolds and contigs was 28.55 Mb and 7.49 Mb, respectively. Based on the mapping results of short reads generated for the paternal and maternal species, each of the 29 chromosomes originating from S. asotus and S. meridionalis was recognized. We recovered nearly 94% and 96% of the total length of S. asotus and S. meridionalis. BUSCO assessments and mapping analyses suggested that both genomes had high completeness and accuracy. Further analyses demonstrated the high collinearity between S. asotus, S. meridionalis, and the related Pelteobagrus fulvidraco. Comparison of the two genomes with that assembled only using the short reads from non-hybrid parental species detected a small portion of sequences that may be incorrectly assigned to the different species. We supposed that at least part of these situations may have resulted from mitotic recombination. The strategy of sequencing the F1 hybrid genome can recover the vast majority of the parental genomes and may improve the assembly of complex genomes.

Prenatal diagnosis of partial monosomy 8p (8p23.2→pter) and partial trisomy 15q (15q21.2→qter) and incidental detection of a familial chromosome translocation of paternal origin in a pregnancy associated with increased nuchal translucency and an abnormal maternal serum screening result.

OBJECTIVE: We present partial monosomy 8p (8p23.2→pter) and partial trisomy 15q (15q21.2→qter) and incidental detection of a familial chromosome translocation of paternal origin in a pregnancy associated with increased nuchal translucency (NT) and an abnormal maternal serum screening result. CASE REPORT: A 29-year-old primigravid woman underwent chorionic villus sampling (CVS) at 13 weeks of gestation because of an increased NT thickness of 3.2 mm at 12 weeks of gestation and an abnormal maternal serum screening for Down syndrome result with a calculated risk of 1/29. Her husband was 33 years old, and there was no family history of congenital malformations. CVS revealed a derived chromosome 8 or der(8). Cytogenetic analysis of the parents revealed a karyotype of 46,XY,t(8;15)(p21.3;q13) in the father and a karyotype of 46,XX in the mother. The CVS result was 46,XY,der(8)t(8;15)(p21.3;q13)pat. The woman requested for amniocentesis at 16 weeks of gestation. Array comparative genomic hybridization (aCGH) analysis on the DNA extracted from uncultured amniocytes revealed a result of arr 8p23.3p23.2 (191,530-2,625,470) × 1.0, arr 15q21.2q26.3 (50,903,432-102,338,129) × 3.0 with a 2.434-Mb deletion of 8p23.3-p23.2 including DLGAP2, CLN8 and ARHGEF10, and a 51.435-Mb duplication of 15q21.2-q26.3 including CYP19A1 and IGF1R. Conventional cytogenetic analysis of cultured amniocytes revealed the result of 46,XY,der(8) t(8;15)(p23.2;q21.2)pat in the fetus. The pregnancy was subsequently terminated, and a malformed fetus was delivered with characteristic craniofacial dysmorphism. CONCLUSION: Maternal serum screening and NT screening may incidentally detect familial unbalanced reciprocal translocations, and aCGH analysis is useful for a precise determination of the breakpoints of the translocation and the involvement of the related genes under such a circumstance.

Prenatal diagnosis of a 15q11.2-q14 deletion of paternal origin associated with increased nuchal translucency, mosaicism for de novo multiple unbalanced translocations involving 15q11-q14, 5qter, 15qter, 17pter and 3qter and Prader-Willi syndrome.

OBJECTIVE: We present prenatal diagnosis of a 15q11.2-q14 deletion of paternal origin associated with increased nuchal translucency (NT), mosaicism for de novo multiple unbalanced translocations involving 15q11-q14, 5qter, 15qter, 17pter and 3qter, and Prader-Willi syndrome (PWS). CASE REPORT: A 32-year-old, primigravid woman underwent amniocentesis at 18 weeks of gestation because of an increased NT thickness of 5.6 mm and abnormal maternal serum screening results in the first trimester. The pregnancy was conceived by in vitro fertilization and embryo transfer. Amniocentesis revealed a karyotype of 45,XX,der(5)t(5;15)(q35;q14),-15 [16]/45,XX,-15,der(17)t(15;17)(q14;p13)[3]/45,XX,der(15)t(15;15)(q35;q14),-15[2]. The parental karyotypes were normal. Prenatal ultrasound findings were unremarkable. Array comparative genomic hybridization (aCGH) analysis on the DNA extracted from cultured amniocytes revealed the result of arr 15q11.2q14 (22,765,628-38,651,755) × 1.0 [GRCh37 (hg19)] with a 15.886-Mb 15q11.2-q14 deletion encompassing TUBGCP5, CYFIP1, NIPA2, NIPA1, SNRPN, SNURF, SNORD116-1, IPW, UBE3A, ACTC1 and MEIS2. The pregnancy was subsequently terminated, and a malformed fetus with facial dysmorphism was delivered. The cord blood had a karyotype of 45,XX,der(5)t(5;15)(q35;q14),-15[46]/45,XX,der(3)t(3;15) (q29;q14),-15[2]/45,XX,-15,der(17)t(15;17)(q14;p13)[2]. The placenta had a karyotype of 45,XX,der(5) t(5;15)(q35;q14),-15. Polymorphic DNA marker analysis confirmed a paternal origin of the proximal 15q deletion. CONCLUSION: Increased NT and abnormal maternal serum screening results may prenatally be associated with PWS. Chromosome 15 rearrangements in PWS include mosaicism for de novo multiple unbalanced translocations.

Molecular cytogenetic characterization of a de novo chromosome 1q41-q42.11 microdeletion of paternal origin in a 15-year-old boy with mental retardation, developmental delay, autism and congenital heart defects.

OBJECTIVE: We present molecular cytogenetic characterization of a de novo chromosome 1q41-q42.11 microdeletion of paternal origin in a mentally retarded child of a family requesting for genetic counseling of the future pregnancy. CASE REPORT: A 43-year-old, gravida 1, para 1, woman, who had a 15-year-old son with mental retardation, planned to have another normal child and requested for genetic counseling of the future pregnancy. Her husband was 48 years old. The 15-year-old boy had a body height of 148 cm (<3rd centile) and a body weight of 40 Kg (<35th centile). He had facial dysmorphism, mental retardation, scoliosis, abnormal gaits, tetralogy of Fallot, pulmonary stenosis and autism but did not have any history of epilepsy. Cytogenetic analysis of the boy and the parents revealed normal karyotypes. Array comparative genomic hybridization (aCGH) analysis of the family revealed a de novo 2.028-Mb 1q41-q42.11 microdeletion, or arr 1q41q42.11 (222,571,596-224,599,234) × 1.0 [GRCh37 (hg19)], encompassing 13 Online Mendelian Inheritance in Man (OMIM) genes including DISP1, SUSD4, FBXO28, TP53BP2 and WDR26 in the child. Quantitative fluorescent polymerase chain reaction analysis confirmed a paternal origin of the deletion. Fluorescence in situ hybridization analysis confirmed a 1q41 deletion. CONCLUSION: Genetic counseling of the parents who have a previous child with mental retardation and who wish to have another normal child in the future pregnancy should include genetic studies, and aCGH is useful under such a circumstance.

Paternal Inheritance of Bisphenol A Cardiotoxic Effects: The Implications of Sperm Epigenome.

Parental exposure to bisphenol A (BPA) has been linked to a greater incidence of congenital diseases. We have demonstrated that BPA induces in zebrafish males an increase in the acetylation of sperm histones that is transmitted to the blastomeres of the unexposed progeny. This work is aimed to determine whether histone hyperacetylation promoted by paternal exposure to BPA is the molecular mechanism underlying the cardiogenesis impairment in the descendants. Zebrafish males were exposed to 100 and 2000 µg/L BPA during early spermatogenesis and mated with non-exposed females. We analyzed in the progeny the expression of genes involved in cardiogenesis and the epigenetic profile. Once the histone hyperacetylation was confirmed, treatment with epigallocatechin gallate (EGCG), an inhibitor of histone acetyltransferases, was assayed on F1 embryos. Embryos from males exposed to 2000 µg/L BPA overexpressed the transcription factor hand2 and the receptor esr2b, showing their own promoters-as well as that of kat6a-an enrichment in H3K9ac. In embryos treated with EGCG, both gene expression and histone acetylation (global and specific) returned to basal levels, and the phenotype was recovered. As shown by the results, the histone hyperacetylated landscape promoted by BPA in the sperm alters the chromatin structure of the progeny, leading to the overexpression of the histone acetyltransferase and genes involved in cardiogenesis.

Genetic Variation in Parental Effects Contributes to the Evolutionary Potential of Prey Responses to Predation Risk.

AbstractDespite the ubiquity of parental effects and their potential effect on evolutionary dynamics, their contribution to the evolution of predator-prey interactions remains poorly understood. Using quantitative genetics, here we demonstrate that parental effects substantially contribute to the evolutionary potential of larval antipredator responses in a leaf beetle (Leptinotarsa decemlineata). Previous research showed that larger L. decemlineata larvae elicit stronger antipredator responses, and mothers perceiving predators improved offspring responses by increasing intraclutch cannibalism-an extreme form of offspring provisioning. We now report substantial additive genetic variation underlying maternal ability to induce intraclutch cannibalism, indicating the potential of this adaptive maternal effect to evolve by natural selection. We also show that paternal size, a heritable trait, affected larval responses to predation risk but that larval responses themselves had little additive genetic variation. Together, these results demonstrate how larval responses to predation risk can evolve via two types of parental effects, both of which provide indirect sources of genetic variation for offspring traits.

Estimation of Parental Effects Using Polygenic Scores.

Offspring resemble their parents for both genetic and environmental reasons. Understanding the relative magnitude of these alternatives has long been a core interest in behavioral genetics research, but traditional designs, which compare phenotypic covariances to make inferences about unmeasured genetic and environmental factors, have struggled to disentangle them. Recently, Kong et al. (2018) showed that by correlating offspring phenotypic values with the measured polygenic score of parents' nontransmitted alleles, one can estimate the effect of "genetic nurture"-a type of passive gene-environment covariation that arises when heritable parental traits directly influence offspring traits. Here, we instantiate this basic idea in a set of causal models that provide novel insights into the estimation of parental influences on offspring. Most importantly, we show how jointly modeling the parental polygenic scores and the offspring phenotypes can provide an unbiased estimate of the variation attributable to the environmental influence of parents on offspring, even when the polygenic score accounts for a small fraction of trait heritability. This model can be further extended to (a) account for the influence of different types of assortative mating, (b) estimate the total variation due to additive genetic effects and their covariance with the familial environment (i.e., the full genetic nurture effect), and (c) model situations where a parental trait influences a different offspring trait. By utilizing structural equation modeling techniques developed for extended twin family designs, our approach provides a general framework for modeling polygenic scores in family studies and allows for various model extensions that can be used to answer old questions about familial influences in new ways.

Direct and Indirect Effects of Maternal, Paternal, and Offspring Genotypes: Trio-GCTA.

Indirect genetic effects from relatives may result in misleading quantifications of heritability, but can also be of interest in their own right. In this paper we propose Trio-GCTA, a model for separating direct and indirect genetic effects when genome-wide single nucleotide polymorphism data have been collected from parent-offspring trios. The model is applicable to phenotypes obtained from any of the family members. We discuss appropriate parameter interpretations and apply the method to three exemplar phenotypes: offspring birth weight, maternal relationship satisfaction, and paternal body-mass index, using real data from the Norwegian Mother, Father and Child Cohort Study (MoBa).

Modeling Parent-Specific Genetic Nurture in Families with Missing Parental Genotypes: Application to Birthweight and BMI.

Disaggregation and estimation of genetic effects from offspring and parents has long been of interest to statistical geneticists. Recently, technical and methodological advances have made the genome-wide and loci-specific estimation of direct offspring and parental genetic nurture effects more possible. However, unbiased estimation using these methods requires datasets where both parents and at least one child have been genotyped, which are relatively scarce. Our group has recently developed a method and accompanying software (IMPISH; Hwang et al. in PLoS Genet 16:e1009154, 2020) which is able to impute missing parental genotypes from observed data on sibships and estimate their effects on an offspring phenotype conditional on the effects of genetic transmission. However, this method is unable to disentangle maternal and paternal effects, which may differ in magnitude and direction. Here, we introduce an extension to the original IMPISH routine which takes advantage of all available nuclear families to impute parent-specific missing genotypes and obtain asymptotically unbiased estimates of genetic effects on offspring phenotypes. We apply this this method to data from related individuals in the UK Biobank, showing concordance with previous estimates of maternal genetic effects on offspring birthweight. We also conduct the first GWAS jointly estimating offspring-, maternal-, and paternal-specific genetic effects on body-mass index.

Tetrasomy of 11q13.4-q14.3 due to an intrachromosomal triplication associated with paternal uniparental isodisomy for 11q14.3-qter, intrauterine growth restriction, developmental delay, corpus callosum dysgenesis, microcephaly, congenital heart defects and facial dysmorphism.

OBJECTIVE: We present tetrasomy of 11q13.4-q14.3 due to an intrachromosomal triplication associated with paternal isodisomy of uniparental disomy (iso-UPD) for 11q14.3-qter and multiple abnormalities. CASE REPORT: A 30-year-old primigravid woman was found to have intrauterine growth restriction (IUGR) in the fetus since 28 weeks of gestation, and a 2056-g baby was delivered at 38 weeks of gestation with fetal distress. The baby postnatally manifested hypotonia, microcephaly, facial dysmorphism of micrognathia, retrognathia and low-set ears, ventricular septal defect, atrial septal defect, tricuspid regurgitation and corpus callosum dysgenesis. A single nucleotide polymorphism (SNP) array comparative genomic hybridization analysis on the DNA extracted from the peripheral blood revealed the result of arr 11q13.4q14.3 (71,567,724-89,547,851) × 4, arr 11q14.3q25 (89,466,484-134,942,626) hmz [GRCh37 (hg19)] with a 17.980-Mb triplication of 11q13.4-q14.3 encompassing the genes of GRM5 and MAP6, and loss of heterozygosity for a 45.476-Mb region of 11q14.3-qter consistent with iso-UPD for 11q14.3-qter. Polymorphic DNA marker analysis confirmed paternal iso-UPD for 11q14.3-qter. Cytogenetic analysis of the blood revealed a karyotype of 46,XY,trp(11) (q13.4q14.3). The parental karyotypes were normal. When follow-ups at age 2 years, the neonate manifested physical and psychomotor developmental delay and intellectual disability. CONCLUSION: Tetrasomy 11q13.4-q14.3 may present the phenotype of IUGR, developmental delay, corpus callosum dysgenesis, microcephaly, congenital heart defects and facial dysmorphism.

"Distribution of paternal lineages in Mestizo populations throughout Mexico: an in silico study based on Y-STR haplotypes".

The Mexican-Mestizo population arose following European contact with the Americas due to the admixture of principally Spaniards, Native Americans, and Africans around 500 years ago. Because the paternal lineage distribution of the Mexican population has been poorly investigated, this study inferred the haplogroups of ten populations based on 1859 haplotypes (Y-STR data) using two haplogroup predictor programs. In the Mexican population sample, we found predominantly European ancestry (50.1%), followed by Native American (32.5%), Eurasian (13.4%), African (2.1%), East African-South Eurasian (1.3%), and Asian (0.6%) ancestries. In general, our results support a contrary north-to-south gradient throughout the Mexican territory of European and Native-American ancestries, respectively. Moreover, the presence of West-European R1b and Sub-Saharan African E1b1a haplogroups agrees with historical and genetic data of gene flow during the European conquest. This study represents the effort to analyze these paternal lineages on a large scale by taking advantage of Y-STR haplotype data to determine the distribution and ancestry proportions in this country.