New insights into the (epi)genetics of twinning.

Spontaneous dizygotic (DZ) twins, i.e. twins conceived without the use of ARTs, run in families and their prevalence varies widely around the globe. In contrast, monozygotic (MZ) twins occur at a constant rate across time and geographical regions and, with some rare exceptions, do not cluster in families. The leading hypothesis for MZ twins, which arise when a zygote splits during preimplantation stages of development, is random occurrence. We have found the first series of genes underlying the liability of being the mother of DZ twins and have shown that being an MZ twin is strongly associated with a stable DNA methylation signature in child and adult somatic tissues. Because identical twins keep this molecular signature across the lifespan, this discovery opens up completely new possibilities for the retrospective diagnosis of whether a person is an MZ twin whose co-twin may have vanished in the early stages of pregnancy. Here, we summarize the gene finding results for mothers of DZ twins based on genetic association studies followed by meta-analysis, and further present the striking epigenetic results for MZ twins.

Amplitude-integrated electroencephalography showed no differences in cerebral activity between preterm singletons and twins in the first 4 weeks of life.

AIM: Genetic influences on cerebral activity have been described previously, but data are scarce in preterms. We aimed to investigate whether a genetic influence causes amplitude-integrated electroencephalography (aEEG) signals to differ between singletons and twin preterm newborns. METHODS: This was a retrospective single-centre study conducted at Innsbruck Medical University Hospital, Austria. Preterm infants born before 32 weeks of gestation between 6 November 2010 and 6 December 2022 were eligible for the study. The aEEG was analysed for the total maturation score, its component scores and the number of sleep-wake cycles per hour. RESULTS: We enrolled 240 preterm twin infants (57.5% male) with a mean gestational age of 30 (range: 24-32) weeks and a mean birth weight of 1324 (range: 600-2116) grams. We compared 240 singleton matched preterms. No differences were found between preterm singletons and twin preterm infants regarding the total maturation and component scores, or the number of sleep-wake cycles. aEEG showed no difference between monozygotic and dizygotic twins. CONCLUSION: Compared to singletons, twin infants born preterm showed no differences in aEEG signals in the first 4 weeks of life. Future studies should include more complex non-invasive functional neuroimaging methods to gain more insight into this important topic.

Frameshift coding sequence variants in the LPL gene: identification of two novel events and exploration of the genotype-phenotype relationship for variants reported to date.

BACKGROUND: Lipoprotein lipase (LPL) is the rate-limiting enzyme for triglyceride hydrolysis. Homozygous or compound heterozygous LPL variants cause autosomal recessive familial chylomicronemia syndrome (FCS), whereas simple heterozygous LPL variants are associated with hypertriglyceridemia (HTG) and HTG-related disorders. LPL frameshift coding sequence variants usually cause complete functional loss of the affected allele, thereby allowing exploration of the impact of different levels of LPL function in human disease. METHODS: All exons and flanking intronic regions of LPL were Sanger sequenced in patients with HTG-related acute pancreatitis (HTG-AP) or HTG-AP in pregnancy. Previously reported LPL frameshift coding sequence variants were collated from the Human Gene Mutation Database and through PubMed keyword searching. Original reports were manually evaluated for the following information: zygosity status of the variant, plasma LPL activity of the variant carrier, disease referred for genetic analysis, patient's age at genetic analysis, and patient's disease history. SpliceAI was employed to predict the potential impact of collated variants on splicing. RESULTS: Two novel rare variants were identified, and 53 known LPL frameshift coding sequence variants were collated. Of the 51 variants informative for zygosity, 30 were simple heterozygotes, 12 were homozygotes, and 9 were compound heterozygotes. Careful evaluation of the 55 variants with respect to their clinical and genetic data generated several interesting findings. First, we conclude that 6-7% residual LPL function could significantly delay the age of onset of FCS and reduce the prevalence of FCS-associated syndromes. Second, whereas a large majority of LPL frameshift coding sequence variants completely disrupt gene function through their "frameshift" nature, a small fraction of these variants may act wholly or partly as "in-frame" variants, leading to the generation of protein products with some residual LPL function. Third, we identified two candidate LPL frameshift coding sequence variants that may retain residual function based on genotype-phenotype correlation or SpliceAI-predicted data. CONCLUSIONS: This study reported two novel LPL variants and yielded new insights into the genotype-phenotype relationship as it pertains to LPL frameshift coding sequence variants.

Iranian school-aged twin registry: preliminary reports and project progress.

BACKGROUND: National Persian school-aged twin registry was established to provide a platform for twin studies. In this report, we describe defining registry characteristics, database design, and preliminary results regarding gathered data in the first phase of the registry program. METHOD: Through focus group discussions, the required data elements to design the database and data collection process were defined. First, a list of twins in school-aged groups was retrieved from the electronic database of the Ministry of Education. Tehran schools were selected for the first phase of our registry. Standard "Pea-in-Pods" questionnaire and twins' similarity questionnaires were filled out by the parents themselves in addition to demographic information. Data were analyzed using SPSS v.22. RESULTS: The first national school-aged twin registry was established in 2018. Firstly, the required data sets and data collection process were defined using focus group discussions. At the country level, the initial information on 189,738 students was retrieved from the national database of the Ministry of Education. They were born between 2003 and 2017, of which 94,997 are boys (50.1%) and 94,741 are girls (49.9%). Of them, a total of 5,642 pairs of school-aged twins participated in the first phase of our program. Our sample size comprised 9772 twins, 906 triples, and 92 quadruplets. The analysis of the zygosity questionnaire showed that 14% of twin pairs were identified as monozygotic twins. CONCLUSION: Recruiting school-aged twins through school health assistants leads to high enrollment and decreasing costs for the twin registry. The study showed a high rate of dizygotic twins that need to be verified by twin bio-sample in the next phase of studies.

Development of a facile genetic transformation system for the Spanish elite rice paella genotype Bomba.

We report the development of an efficient and reproducible genetic transformation system for the recalcitrant Spanish elite rice paella genotype, Bomba. Preconditioned embryos derived from dry seeds were bombarded with gold particles carrying a plasmid containing a screenable and a selectable marker. We confirmed integration and expression of hpt and gusA in the rice genome. Transformation frequency was ca: 10% in several independent experiments. We show Mendelian inheritance of the input transgenes and zygosity determination of the transgenic lines in the T1 generation. A unique and critical step for the regeneration of plants from transformed tissue was shading during the early stages of regeneration, combined with a specific cytokinin:auxin ration at the onset of shifting callus to regeneration media.

RHD 1227 A and hybrid Rhesus box analysis in Thai RhD+ and RhD- blood donors: Prevalence, RHD zygosity, and molecular screening.

BACKGROUND AND OBJECTIVES: DEL (D-elute) red blood cells (RBCs) are typed as D- by routine serological methods, as they carry a very weak form of D variant. Asia type DEL (c.1227 G>A) is the most prevalent DEL allele in East Asian populations that can lead to alloimmunization in D negative transfusion recipients. This study aimed to screen D+ and D- Thai blood donors for the Asia type DEL and its zygosity. MATERIALS AND METHODS: Blood samples of 723 D+ , and 191 D- Thai blood donors were collected. D antigen was typed by the routine serological method and adsorption-elution test to screen DEL phenotype. The hybrid Rhesus box, RHD 1227 G, RHD 1227 A and RHD exon 4 were analyzed with polymerase chain reaction using sequence specific primers, PCR-SSP. RESULTS: Among 191 D- blood donors, 52 (27.2%) RHD 1227 A allele carriers were detected, and 39 out of these 52 (75.0%) were positive for the hybrid Rhesus box (i.e. hemizygous RHD 1227 A). The remaining carriers were RHD 1227 A homozygous. RHD zygosity analysis in Thai D+ blood donors showed that only 4% (29/723) had a Dd genotype (hemizygous RHD 1227 G). Five (0.69%) blood donors were detected with RHD 1227 A alleles among 723 D+ blood donors. They were all G/A heterozygous at the RHD 1227 site. CONCLUSION: This study indicates that the high prevalence of RHD 1227 A allele among serologically apparent D- blood donors in Thais. Furthermore, the screening of hybrid Rhesus box, RHD 1227 A combined with RHD exon 4 is useful for analyses of Asia type DEL and its zygosity.

HLA Zygosity Increases Risk of Hepatitis B Virus-Associated Hepatocellular Carcinoma.

BACKGROUND: Diversity in the HLA genes might be associated with disease outcomes-the heterozygote advantage hypothesis. We tested this hypothesis in relation to hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC). METHODS: We utilized DNA from > 10 000 Taiwanese individuals with current or past HBV infection to examine the association between HLA diversity and critical natural history steps in the progression from HBV infection to HCC. Individuals were classified as homozygotes at a given locus when imputed to carry the same 4-digit allele for the 2 HLA alleles at that locus. RESULTS: Increase in number of homozygous HLA class II loci was associated with an increased risk of chronic HBV infection (Ptrend = 1.18 × 10-7). Among chronic HBV carriers, increase in number of homozygous HLA class II loci was also associated with an increased risk of HBV-associated HCC (Ptrend = .031). For individual HLA loci, HLA-DQB1 homozygosity was significantly associated with HCC risk (adjusted hazard ratio = 1.40; 95% confidence interval, 1.06-1.84). We also found that zygosity affects risk of HCC through its ability to affect viral control. CONCLUSIONS: Homozygosity at HLA class II loci, particularly HLA-DQB1, is associated with a higher risk of HBV-associated HCC.

Pancreas cancer and BRCA: A critical subset of patients with improving therapeutic outcomes.

BACKGROUND: Patients with germline/somatic BRCA1/BRCA2 mutations (g/sBRCA1/2) comprise a distinct biologic subgroup of pancreas ductal adenocarcinoma (PDAC). METHODS: Institutional databases were queried to identify patients who had PDAC with g/sBRCA1/2. Demographics, clinicopathologic details, genomic data (annotation sBRCA1/2 according to a precision oncology knowledge base for somatic mutations), zygosity, and outcomes were abstracted. Overall survival (OS) was estimated using the Kaplan-Meier method. RESULTS: In total, 136 patients with g/sBRCA1/2 were identified between January 2011 and June 2020. Germline BRCA1/2 (gBRCA1/2) mutation was identified in 116 patients (85%). Oncogenic somatic BRCA1/2 (sBRCA1/2) mutation was present in 20 patients (15%). Seventy-seven patients had biallelic BRCA1/2 mutations (83%), and 16 (17%) had heterozygous mutations. Sixty-five patients with stage IV disease received frontline platinum therapy, and 52 (80%) had a partial response. The median OS for entire cohort was 27.6 months (95% CI, 24.9-34.5 months), and the median OS for patients who had stage IV disease was 23 months (95% CI, 19-26 months). Seventy-one patients received a poly(adenosine diphosphate ribose) polymerase (PARP) inhibitor (PARPi), and 52 received PARPi monotherapy. For maintenance PARPi, 10 patients (36%) had a partial response, 12 (43%) had stable disease, and 6 (21%) had progression of disease as their best response. Six patients (21%) received maintenance PARPi for >2 years. For those with stage IV disease who received frontline platinum, the median OS was 26 months (95% CI, 20-52 months) for biallelic patients (n = 39) and 8.66 months (95% CI, 6.2 months to not reached) for heterozygous patients (n = 4). The median OS for those who received PARPi therapy was 26.5 months (95% CI, 24-53 months) for biallelic patients (n = 25) and 8.66 months (95% CI, 7.23 months to not reached) for heterozygous patients (n = 2). CONCLUSIONS: g/sBRCA1/2 mutations did not appear to have different actionable utility. Platinum and PARPi therapies offer therapeutic benefit, and very durable outcomes are observed in a subset of patients who have g/sBRCA1/2 mutations with biallelic status.

The spectrum of brain malformations and disruptions in twins.

Twins have an increased risk for congenital malformations and disruptions, including defects in brain morphogenesis. We analyzed data on brain imaging, zygosity, sex, and fetal demise in 56 proband twins and 7 less affected co-twins with abnormal brain imaging and compared them to population-based data and to a literature series. We separated our series into malformations of cortical development (MCD, N = 39), cerebellar malformations without MCD (N = 13), and brain disruptions (N = 11). The MCD group included 37/39 (95%) with polymicrogyria (PMG), 8/39 (21%) with pia-ependymal clefts (schizencephaly), and 15/39 (38%) with periventricular nodular heterotopia (PNH) including 2 with PNH but not PMG. Cerebellar malformations were found in 19 individuals including 13 with a cerebellar malformation only and another 6 with cerebellar malformation and MCD. The pattern varied from diffuse cerebellar hypoplasia to classic Dandy-Walker malformation. Brain disruptions were seen in 11 individuals with hydranencephaly, porencephaly, or white matter loss without cysts. Our series included an expected statistically significant excess of monozygotic (MZ) twin pairs (22/41 MZ, 54%) compared to population data (482/1448 MZ, 33.3%; p = .0110), and an unexpected statistically significant excess of dizygotic (DZ) twins (19/41, 46%) compared to the literature cohort (1/46 DZ, 2%; p < .0001. Recurrent association with twin-twin transfusion syndrome, intrauterine growth retardation, and other prenatal factors support disruption of vascular perfusion as the most likely unifying cause.

The concordance rate of non-chromosomal congenital malformations in twins based on zygosity: a retrospective cohort study.

OBJECTIVE: To examine the concordance rate of non-chromosomal congenital malformations in twin pairs based on zygosity. DESIGN: Retrospective cohort study. SETTING: A tertiary hospital in Korea. POPULATION: Twin pairs born at Seoul National University Hospital between 2001 and 2019. METHODS: Congenital malformations were diagnosed by postnatal workups of neonates or autopsy in cases of stillborn infants. Zygosity was confirmed by sex, chorionicity and DNA analysis. MAIN OUTCOME MEASURES: Concordance rate of congenital malformations in twin pairs based on zygosity. RESULTS: In total, 3386 twin pairs were included. The risk of a congenital malformation in the index twin increased significantly if the co-twin had the congenital malformation, and the concordance rate was higher in monozygotic (MZ) than in dizygotic (DZ) twins (37.04 versus 16.77, P < 0.001). An increased risk of a congenital malformation in the presence of the same congenital malformation in the co-twin was observed only for malformations of the nervous system, eye/ear/face/neck, circulatory system, cleft lip/palate, genital organs, urinary system and musculoskeletal system. Significantly higher concordance rates in MZ than in DZ twin pairs were observed only for the nervous system (40.00 versus 0.00, P < 0.001), circulatory system (32.97 versus 19.74, P = 0.021), cleft lip/palate (44.44 versus 0.00, P = 0.017) and urinary system (22.22 versus 0.00, P = 0.004), whereas significant differences were not found for the genital organs or musculoskeletal system. CONCLUSIONS: Monozygotic twins had higher concordance rates than DZ twins only in specific organ systems. It may be speculated that nervous system, circulatory system, cleft lip/palate and urinary system are primarily genetically affected. TWEETABLE ABSTRACT: Monozygotic twins had higher concordance rates than dizygotic twins only in specific organ systems.

Digital PCR (dPCR) and qPCR mediated determination of transgene copy number in the forage legume white clover (Trifolium repens).

Obtaining data on transgene copy number is an integral step in the generation of transgenic plants. Techniques such as Southern blot, segregation analysis, and quantitative PCR (qPCR) have routinely been used for this task, in a range of species. More recently, use of Digital PCR (dPCR) has become prevalent, with a measurement accuracy higher than qPCR reported. Here, the relative merits of qPCR and dPCR for transgene copy number estimation in white clover were investigated. Furthermore, given that single copy reference genes are desirable for estimating gene copy number by relative quantification, and that no single-copy genes have been reported in this species, a search and evaluation of suitable reference genes in white clover was undertaken. Results demonstrated a higher accuracy of dPCR relative to qPCR for copy number estimation in white clover. Two genes, Pyruvate dehydrogenase (PDH), and an ATP-dependent protease, identified as single-copy genes, were used as references for copy number estimation by relative quantification. Identification of single-copy genes in white clover will enable the application of relative quantification for copy number estimation of other genes or transgenes in the species. The results generated here validate the use of dPCR as a reliable strategy for transgene copy number estimation in white clover, and provide resources for future copy number studies in this species.

Twin chorionicity and zygosity both vary with maternal age.

Objective: To determine the ratio of dichorionic (DC) to monochorionic (MC) twins by maternal age. Methods: We reviewed all twin pregnancies undergoing first trimester screening (FTS) with nuchal translucency from April 2009 to December 2012 with sonographic determination of chorionicity. Cases were linked to newborn screening (NBS) results and zygosity estimated based on rates of fetal sex discordance. The ratio of DC to MC placentation by maternal age was calculated. Results: We identified 11,351 twin pregnancies with FTS and documented chorionicity. Among these, 7,861 (64.2%) had linked data on FTS and NBS to allow estimation of zygosity based on neonatal sex. Of these, 1,464 (18.6%) were MC and 6,406 (81.4%) DC. The MC twin rate remained constant while the DC twin rate increased with maternal age until 40y. At < 20y, 55% of twin pregnancies were monozygotic (MZ), as compared to 29% at ≥ 40y. Of MZ twins, 38% were DC at < 20y, while 53% were DC at ≥ 40y. Conclusions: Our data suggest a relationship of both zygosity and chorionicity with maternal age. DZ twinning increased with maternal age, while among MZ twins, the proportion that were DC also increased with maternal age.

Determining Zygosity in Infant Twins - Revisiting the Questionnaire Approach.

Accurate zygosity determination is a fundamental step in twin research. Although DNA-based testing is the gold standard for determining zygosity, collecting biological samples is not feasible in all research settings or all families. Previous work has demonstrated the feasibility of zygosity estimation based on questionnaire (physical similarity) data in older twins, but the extent to which this is also a reliable approach in infancy is less well established. Here, we report the accuracy of different questionnaire-based zygosity determination approaches (traditional and machine learning) in 5.5 month-old twins. The participant cohort comprised 284 infant twin pairs (128 dizygotic and 156 monozygotic) who participated in the Babytwins Study Sweden (BATSS). Manual scoring based on an established technique validated in older twins accurately predicted 90.49% of the zygosities with a sensitivity of 91.65% and specificity of 89.06%. The machine learning approach improved the prediction accuracy to 93.10%, with a sensitivity of 91.30% and specificity of 94.29%. Additionally, we quantified the systematic impact of zygosity misclassification on estimates of genetic and environmental influences using simulation-based sensitivity analysis on a separate data set to show the implication of our machine learning accuracy gain. In conclusion, our study demonstrates the feasibility of determining zygosity in very young infant twins using a questionnaire with four items and builds a scalable machine learning model with better metrics, thus a viable alternative to DNA tests in large-scale infant twin studies.

On the origin of zygosity and chorionicity in twinning: evidence from human in vitro fertilization.

Assisted reproduction is presumed to increase monozygotic twin rates, with the possible contribution of laboratory and medical interventions. Monozygotic dichorionic gestations are supposed to originate from the splitting of an embryo during the first four days of development, before blastocyst formation. Single embryo transfers could result in dichorionic pregnancies, currently explained by embryo splitting as described in the worldwide used medical textbooks, or concomitant conception. However, such splitting has never been observed in human in vitro fertilization, and downregulated frozen cycles could also produce multiple gestations. Several models of the possible origins of dichorionicity have been suggested. However, some possible underlying mechanisms observed from assisted reproduction seem to have been overlooked. In this review, we aimed to document the current knowledge, criticize the accepted dogma, and propose new insights into the origin of zygosity and chorionicity.

High-Throughput and Accurate Determination of Transgene Copy Number and Zygosity in Transgenic Maize: From DNA Extraction to Data Analysis.

It is vital to develop high-throughput methods to determine transgene copy numbers initially and zygosity during subsequent breeding. In this study, the target sequence of the previously reported endogenous reference gene hmg was analyzed using 633 maize inbred lines, and two SNPs were observed. These SNPs significantly increased the PCR efficiency, while the newly developed hmg gene assay (hmg-taq-F2/R2) excluding these SNPs reduced the efficiency into normal ranges. The TaqMan amplification efficiency of bar and hmg with newly developed primers was calculated as 0.993 and 1.000, respectively. The inter-assay coefficient of variation (CV) values for the bar and hmg genes varied from 1.18 to 2.94%. The copy numbers of the transgene bar using new TaqMan assays were identical to those using dPCR. Significantly, the precision of one repetition reached 96.7% of that of three repetitions of single-copy plants analyzed by simple random sampling, and the actual accuracy reached 95.8%, confirmed by T1 and T2 progeny. With the high-throughput DNA extraction and automated data analysis procedures developed in this study, nearly 2700 samples could be analyzed within eight hours by two persons. The combined results suggested that the new hmg gene assay developed here could be a universal maize reference gene system, and the new assay has high throughput and high accuracy for large-scale screening of maize varieties around the world.

An extragonadal yolk sac tumor presumed to be of postmeiotic germ cell origin by genetic zygosity analysis via single nucleotide polymorphism array.

An extragonadal yolk sac tumor (YST) is a rare malignant germ cell tumor that usually occurs in childhood. The pathogenesis of extragonadal YST remains largely unknown, especially with regards to its cell of origin. Herein, we report a case of extragonadal YST arising in the uterine round ligament. A 31-year-old Japanese woman, para 2, underwent partial resection of a left-sided, 5-cm, solid inguinal mass. Intraoperative findings showed enlargement of the uterine round ligament in the inguinal canal. Pathological evaluation diagnosed the mass as YST with a mature teratoma (MT) component. The preoperative α-fetoprotein level was markedly elevated, at 24 790 ng/mL. Postoperative magnetic resonance imaging revealed a right ovarian MT and a 3-cm mass remaining in the left lower abdominal wall. The patient underwent total abdominal hysterectomy, bilateral adnexectomy, and left inguinal mass resection. We sampled three frozen tissues (YST, right ovarian MT, and left normal ovary) and performed a single nucleotide polymorphism (SNP) array. Pathological evaluation revealed remnant extragonadal YST in the left inguinal region. The SNP array demonstrated a completely homozygous YST genotype. Copy number variations were gains of 1p, 1q, 2p, 3p, 7p, 8p, 10q, 14q, 18p, 20q, Xp, and Xq and losses of 12q, 20p, and Xq. The right ovarian MT and left normal ovary were partially homozygous and heterozygous, respectively. The evidence suggests that this neoplasm is presumed to be a postmeiotic germ cell origin.

Combining next-generation sequencing and progeny testing for rapid identification of induced recessive and dominant mutations in maize M2 individuals.

Molecular identification of mutant alleles responsible for certain phenotypic alterations is a central goal of genetic analyses. In this study we describe a rapid procedure suitable for the identification of induced recessive and dominant mutations applied to two Zea mays mutants expressing a dwarf and a pale green phenotype, respectively, which were obtained through pollen ethyl methanesulfonate (EMS) mutagenesis. First, without prior backcrossing, induced mutations (single nucleotide polymorphisms, SNPs) segregating in a (M2 ) family derived from a heterozygous (M1 ) parent were identified using whole-genome shotgun (WGS) sequencing of a small number of (M2 ) individuals with mutant and wild-type phenotypes. Second, the state of zygosity of the mutation causing the phenotype was determined for each sequenced individual by phenotypic segregation analysis of the self-pollinated (M3 ) offspring. Finally, we filtered for segregating EMS-induced SNPs whose state of zygosity matched the determined state of zygosity of the mutant locus in each sequenced (M2 ) individuals. Through this procedure, combining sequencing of individuals and Mendelian inheritance, three and four SNPs in linkage passed our zygosity filter for the homozygous dwarf and heterozygous pale green mutation, respectively. The dwarf mutation was found to be allelic to the an1 locus and caused by an insertion in the largest exon of the AN1 gene. The pale green mutation affected the nuclear W2 gene and was caused by a non-synonymous amino acid exchange in encoded chloroplast DNA polymerase with a predicted deleterious effect. This coincided with lower cpDNA levels in pale green plants.

Psychometric and Classification Properties of the Peas in a Pod Questionnaire.

We examined the item properties of the Two Peas Questionnaire (TPQ) among a sample of same-sex twin pairs from the Washington State Twin Registry. With the exception of the 'two peas' item, three of the mistakenness items showed differential item functioning. Results showed that the monozygotic (MZ) and dizygotic (DZ) pairs may differ in their responses on these items, even among those with similar latent traits of similarity and confusability. Upon comparing three classification methods to determine the zygosity of same-sex twins, the overall classification accuracy rate was over 90% using the unit-weighted pair zygosity sum score, providing an efficient and sufficiently accurate zygosity classification. Given the inherent nature of twin-pair similarity, the TPQ is more accurate in the identification of MZ than DZ pairs. We conclude that the TPQ is a generally accurate, but by no means infallible, method of determining zygosity in twins who have not been genotyped.

First Steps of the Mexico Twin Registry (RGMex-MexTR) at the University of Guadalajara.

Despite the well-known relevance of twin studies in the medical and social sciences and the growing number of twin registries throughout the world, Latin America has not fully incorporated into the twin research community. We describe the first steps taken toward developing a twin registry in Mexico: its aim, organization, recruiting potential and main short-term objectives.

The Netherlands Twin Register: Longitudinal Research Based on Twin and Twin-Family Designs.

The Netherlands Twin Register (NTR) is a national register in which twins, multiples and their parents, siblings, spouses and other family members participate. Here we describe the NTR resources that were created from more than 30 years of data collections; the development and maintenance of the newly developed database systems, and the possibilities these resources create for future research. Since the early 1980s, the NTR has enrolled around 120,000 twins and a roughly equal number of their relatives. The majority of twin families have participated in survey studies, and subsamples took part in biomaterial collection (e.g., DNA) and dedicated projects, for example, for neuropsychological, biomarker and behavioral traits. The recruitment into the NTR is all inclusive without any restrictions on enrollment. These resources - the longitudinal phenotyping, the extended pedigree structures and the multigeneration genotyping - allow for future twin-family research that will contribute to gene discovery, causality modeling, and studies of genetic and cultural inheritance.