Maternal Genetic Background Research Articles

Evaluating possible maternal effect lethality and genetic background effects in Naa10 knockout mice.

Amino-terminal (Nt-) acetylation (NTA) is a common protein modification, affecting approximately 80% of all human proteins. The human essential X-linked gene, NAA10, encodes for the enzyme NAA10, which is the catalytic subunit in the N-terminal acetyltransferase A (NatA) complex. There is extensive genetic variation in humans with missense, splice-site, and C-terminal frameshift variants in NAA10. In mice, Naa10 is not an essential gene, as there exists a paralogous gene, Naa12, that substantially rescues Naa10 knockout mice from embryonic lethality, whereas double knockouts (Naa10-/Y Naa12-/-) are embryonic lethal. However, the phenotypic variability in the mice is nonetheless quite extensive, including piebaldism, skeletal defects, small size, hydrocephaly, hydronephrosis, and neonatal lethality. Here we replicate these phenotypes with new genetic alleles in mice, but we demonstrate their modulation by genetic background and environmental effects. We cannot replicate a prior report of "maternal effect lethality" for heterozygous Naa10-/X female mice, but we do observe a small amount of embryonic lethality in the Naa10-/y male mice on the inbred genetic background in this different animal facility.

Interferon-stimulated gene 15 polymorphisms are associated with spontaneous preterm birth in Taiwanese women.

Immune and inflammatory responses are known to be major causes of preterm birth (PTB). The maternal genetic background plays an important role in the development of PTB. Interferon-stimulated gene 15 (ISG15) is an interferon-induced protein which can modulate immune cell activation and function. We aim to study if polymorphisms in the ISG15 gene are associated with spontaneous PTB (sPTB) risk in Taiwanese women. ISG15 rs4615788 C/G, rs1921 G/A, and rs8997 A/G polymorphisms were genotyped in a hospital-based study of 112 women with sPTB and 1120 term controls. The plasma concentrations of ISG15 were determined by enzyme-linked immunosorbent assay. We found the ISG15 rs1921 G-rs8997 A haplotype was associated with decreased risk for PTB (χ2 =6.26, p=.01, pc =.04). The A/G genotype of ISG15 rs8997 polymorphism might have the potential to confer reduced risk of PTB women (χ2 =4.09, p=.04, pc =.08). Spontaneous PTB women displayed higher plasma ISG15 levels compared to term controls (p<.001). The plasma ISG15 levels among pregnant women with rs8997 A/G genotype were found significantly lower compared to G/G genotype (p=.03). Women with the ISG15 rs1921 G-rs8997 A haplotype may associate with spontaneous PTB. These findings provide new insights into the etiology of preterm birth.

The Interactions between Maternal Iron Supplementation and Iron Metabolism-Related Genetic Polymorphisms on Birth Outcomes: A Prospective Study in Chinese

BackgroundThe effect of iron supplementation during pregnancy on birth outcomes may vary with maternal genetic background and needs more investigation. ObjectivesThis prospective study aimed to evaluate the interactions between maternal iron supplementation and iron metabolism-related genetic polymorphisms on birth outcomes. MethodsThis was a substudy from a community-based randomized control trial conducted in Northwest China, which included 860 women from the 2 micronutrient supplementation groups (folic acid [FA] and FA + iron group). Maternal peripheral blood, sociodemographic and health-related information, and neonatal birth outcomes were collected. Six single nucleotide polymorphisms in iron metabolism-related genes were genotyped. The alleles associated with decreased iron/hemoglobin status were used as the effect alleles. The genetic risk score (GRS) that reflected the genetic risk of low iron/hemoglobin status was estimated using the unweighted and weighted methods. Generalized estimating equations with small-sample corrections were applied to evaluate the interactions between iron supplementation and SNPs/GRS on birth outcomes. ResultsThere were significant interactions between maternal iron supplementation and rs7385804 (P = 0.009), rs149411 (P = 0.035), rs4820268 (P = 0.031), the unweighted GRS (P = 0.018), and the weighted GRS (P = 0.009) on birth weight. Compared with FA supplementation only, FA + iron supplementation significantly increased birth weight among women with more effect alleles in rs7385804 (β: 88.8 g, 95% CI: 9.2, 168.3) and the GRSs (the highest unweighted GRS, β: 135.5 g, 95% CI: 7.7, 263.4; the highest weighted GRS, β: 145.9 g, 95% CI: 43.4, 248.5); it had a trend of decreasing birth weight and increasing low birth weight risk among women with fewer effect alleles. ConclusionsIn our population, maternal genetic background related to iron metabolism plays a significant role in determining the efficacy of iron supplementation. Routine iron supplementation could be more beneficial to fetal weight growth among mothers with higher genetic risk for low iron/hemoglobin status.

Evaluation of Maternal Genetic Background of Two Hungarian Autochthonous Sheep Breeds Coming from Different Geographical Directions.

Simple SummaryBy the 19th century, adequately producing, independent domestic animal breeds had developed in many regions around the globe. However, from the middle of the 20th century they have largely been replaced by high-performing, specialized, single-purpose cosmopolitan breeds. Breed maintenance is an activity aimed at rescuing old breeds from the threat of extinction. This process includes recording the valuable traits of a rare breed, specific diversity conservation selection, and utilization in the original production environment. Additionally, it deals with the history of breeds and the study of their genetic makeup. The aim of this paper is to evaluate the maternal genetic background of two autochthonous sheep breeds in Hungary.The aim of our research was the evaluation of the maternal genetic background of two Hungarian autochthonous sheep breeds of different geographical origin. A major argument for the preservation of endangered animal breeds is their documented past and historical importance. These also include the registration of pedigree data. This is the first study to evaluate and compare Tsigai and Cikta sheep in Hungary. Our investigation is based on two complete sequences of mitochondrial DNA (cytochrome b gene and control region). Our research was performed on these two sheep breeds with markedly different breed histories and breed characteristics to determine a possible common maternal genetic background, as ultimately the origin of both breeds can be traced back to Asia Minor. Between 2015 and 2017, a total of 203 biological samples were taken using a newly introduced founder sampling method. We found that the prevailing haplogroup B accounted for over 80% of both breeds, strengthening the common ancestral root. However, the pairwise genetic differentiation estimates (KST) calculated using the sequence-based statistics for cytochrome b gene and control region were 0.034 and 0.021, respectively (both at level p < 0.05); thus, revealing genetic differentiation in both sequences between the Tsigai and Cikta. We note that the known different history of the breeds is clearly justified by the currently studied deviations in their maternal genetic background.

Maternal background alters the penetrance of growth phenotypes and sex-specific placental adaptation of offspring sired by alcohol-exposed males.

Epigenetic mechanisms of paternal inheritance are an emerging area of interest in our efforts to understand fetal alcohol spectrum disorders. In rodent models examining maternal alcohol exposures, different maternal genetic backgrounds protect or sensitize offspring to alcohol‐induced teratogenesis. However, whether maternal background can mitigate sperm‐inherited alterations in developmental programming and modify the penetrance of growth defects induced by preconception paternal alcohol exposures remains unaddressed. In our previous studies examining pure C57Bl/6J crosses, the offspring of alcohol‐exposed sires exhibited fetal growth restriction, enlarged placentas, and decreased placental efficiency. Here, we find that in contrast to our previous studies, the F1 offspring of alcohol‐exposed C57Bl/6J sires and CD‐1 dams do not exhibit fetal growth restriction, with male fetuses developing smaller placentas and increased placental efficiencies. However, in these hybrid offspring, preconception paternal alcohol exposure induces sex‐specific changes in placental morphology. Specifically, the female offspring of alcohol‐exposed sires displayed structural changes in the junctional and labyrinth zones, along with increased placental glycogen content. These changes in placental organization are accompanied by female‐specific alterations in the expression of imprinted genes Cdkn1c and H19. Although male placentae do not display overt changes in placental histology, using RNA‐sequencing, we identified programmed alterations in genes regulating oxidative phosphorylation, mitochondrial function, and Sirtuin signaling. Collectively, our data reveal that preconception paternal alcohol exposure transmits a stressor to developing offspring, that males and females exhibit distinct patterns of placental adaptation, and that maternal genetic background can modulate the effects of paternal alcohol exposure.

Maternal genetic origin of the late and final Neolithic human populations from present-day Poland.

We aim to identify maternal genetic affinities between the Middle to Final Neolithic (3850-2300 BC) populations from present-day Poland and possible genetic influences from the Pontic steppe. We conducted ancient DNA studies from populations associated with Złota, Globular Amphora, Funnel Beaker, and Corded Ware cultures (CWC). We sequenced genomic libraries on Illumina platform to generate 86 complete ancient mitochondrial genomes. Some of the samples were enriched for mitochondrial DNA using hybridization capture. The maternal genetic composition found in Złota-associated individuals resembled that found in people associated with the Globular Amphora culture which indicates that both groups likely originated from the same maternal genetic background. Further, these two groups were closely related to the Funnel Beaker culture-associated population. None of these groups shared a close affinity to CWC-associated people. Haplogroup U4 was present only in the CWC group and absent in Złota group, Globular Amphora, and Funnel Beaker cultures. The prevalence of mitochondrial haplogroups of Neolithic farmer origin identified in Early, Middle and Late Neolithic populations suggests a genetic continuity of these maternal lineages in the studied area. Although overlapping in time - and to some extent - in cultural expressions, none of the studied groups (Złota, Globular Amphora, Funnel Beaker), shared a close genetic affinity to CWC-associated people, indicating a larger extent of cultural influence from the Pontic steppe than genetic exchange. The higher frequency of haplogroup U5b found in populations associated with Funnel Beaker, Globular Amphora, and Złota cultures suggest a gradual maternal genetic influx from Mesolithic hunter-gatherers. Moreover, presence of haplogroup U4 in Corded Ware groups is most likely associated with the migrations from the Pontic steppe at the end of the Neolithic and supports the observed genetic distances.

Whole-exome sequencing reveals insights into genetic susceptibility to Congenital Zika Syndrome.

Congenital Zika Syndrome (CZS) is a critical illness with a wide range of severity caused by Zika virus (ZIKV) infection during pregnancy. Life-threatening neurodevelopmental dysfunctions are among the most common phenotypes observed in affected newborns. Risk factors that contribute to susceptibility and response to ZIKV infection may be related to the virus itself, the environment, and maternal genetic background. Nevertheless, the newborn’s genetic contribution to the critical illness is still not elucidated. Here, we aimed to identify possible genetic variants as well as relevant biological pathways that might be associated with CZS phenotypes. For this purpose, we performed a whole-exome sequencing in 40 children born to women with confirmed exposure to ZIKV during pregnancy. We investigated the occurrence of rare harmful single-nucleotide variants (SNVs) possibly associated with inborn errors in genes ontologically related to CZS phenotypes. Moreover, an exome-wide association analysis was also performed using a case-control design (29 CZS cases and 11 controls), for both common and rare variants. Five out of the 29 CZS patients harbored known pathogenic variants likely to contribute to mild to severe manifestations observed. Approximately, 30% of affected individuals carried at least one pathogenic or likely pathogenic SNV in genes candidates to play a role in CZS. Our common variant association analysis detected a suggestive protective effect of the rs2076469 in DISP3 gene (p-value: 1.39 x 10−5). The IL12RB2 gene (p-value: 2.18x10-11) also showed an unusual distribution of nonsynonymous rare SNVs in control samples. Finally, genes harboring harmful variants are involved in processes related to CZS phenotypes such as neurological development and immunity. Therefore, both rare and common variations may be likely to contribute as the underlying genetic cause of CZS susceptibility. The variations and pathways identified in this study may also have implications for the development of therapeutic strategies in the future.

Personalized Nutrition Approach in Pregnancy and Early Life to Tackle Childhood and Adult Non-Communicable Diseases.

The development of childhood and adult non-communicable diseases (NCD) is associated with environmental factors, starting from intrauterine life. A new theory finds the roots of epigenetic programming in parental gametogenesis, continuing during embryo development, fetal life, and finally in post-natal life. Maternal health status and poor nutrition are widely recognized as implications in the onset of childhood and adult diseases. Early nutrition, particularly breastfeeding, also plays a primary role in affecting the health status of an individual later in life. A poor maternal diet during pregnancy and lack of breastfeeding can cause a nutrient deficiency that affects the gut microbiota, and acts as a cofactor for many pathways, impacting the epigenetic controls and transcription of genes involved in the metabolism, angiogenesis, and other pathways, leading to NCDs in adult life. Both maternal and fetal genetic backgrounds also affect nutrient adsorption and functioning at the cellular level. This review discusses the most recent evidence on maternal nutrition and breastfeeding in the development of NCD, the potentiality of the omics technologies in uncovering the molecular mechanisms underlying it, with the future prospective of applying a personalized nutrition approach to prevent and treat NCD from the beginning of fetal life.

Polymorphic variants in Sweet and Umami taste receptor genes and birthweight

The first thousand days of life from conception have a significant impact on the health status with short, and long-term effects. Among several anthropometric and maternal lifestyle parameters birth weight plays a crucial role on the growth and neurological development of infants. Recent genome wide association studies (GWAS) have demonstrated a robust foetal and maternal genetic background of birth weight, however only a small proportion of the genetic hereditability has been already identified. Considering the extensive number of phenotypes on which they are involved, we focused on identifying the possible effect of genetic variants belonging to taste receptor genes and birthweight. In the human genome there are two taste receptors family the bitter receptors (TAS2Rs) and the sweet and umami receptors (TAS1Rs). In particular sweet perception is due to a heterodimeric receptor encoded by the TAS1R2 and the TAS1R3 gene, while the umami taste receptor is encoded by the TAS1R1 and the TAS1R3 genes. We observed that carriers of the T allele of the TAS1R1-rs4908932 SNPs showed an increase in birthweight compared to GG homozygotes Coeff: 87.40 (35.13–139.68) p-value = 0.001. The association remained significant after correction for multiple testing. TAS1R1-rs4908932 is a potentially functional SNP and is in linkage disequilibrium with another polymorphism that has been associated with BMI in adults showing the importance of this variant from the early stages of conception through all the adult life.

Insights into Lake Baikal's ancient populations based on genetic evidence from the Early Neolithic Shamanka II and Early Bronze Age Kurma XI cemeteries

Abstract: Although previous ancient DNA research has contributed to the investigation of middle Holocene culture history and population dynamics in the Cis-Baikal, most of this work has been limited to the Angara valley and southwest Baikal, with only restricted genetic analysis of skeletal materials from the Little Sea microregion. In this paper, we expand upon initial findings by analyzing new mtDNA results from the EN/EBA Kurma XI cemetery (Little Sea area) and the EN Shamanka II cemetery (southwest Baikal). Our results not only contribute to the regional dataset, but also challenge previous findings. First, haplogroup Z was found for the first time in the ancient population of Cis-Baikal. Second, our data provide tentative support for the idea that an exogamous and/or patrilocal marriage pattern might be detectable at the Early Bronze Age cemetery Kurma XI. Third, our results indicate that the EN population of Cis-Baikal may not be as homogeneous in maternal origin as was previously suggested. Similarly, there seems to be less continuity between the Late Neolithic and Early Bronze age samples than previously thought, which further justifies the separation of these groups for future analyses. Finally, our data indicate that the maternal genetic background of the Early Bronze Age sample from Kurma XI is closer to that of known Early Neolithic groups than it is to those from the Late Neolithic or Early Bronze Age. This observation is surprising and, if correct, would seem to directly contradict the previous suggestion of a Middle Neolithic genetic discontinuity. These new findings complicate our understanding of the relationships between middle Holocene populations in the Cis-Baikal.

Changes in human milk fatty acid composition and maternal lifestyle-related factors over a decade: a comparison between the two Ulm Birth Cohort Studies.

Human milk fatty acid composition varies during lactation and is influenced by maternal diet, maternal lifestyle-related factors and genetic background. This is one of the first studies to investigate a period effect, that is, the impact of lifestyle-related changes on human milk fatty acid composition, in two different cohorts. Lactating women were recruited from the general population a decade apart in Ulm, Germany, using similar methodology. Human milk samples collected 6 weeks postpartum were analysed (Ulm Birth Cohort Study (UBCS (2000)), n 567; Ulm SPATZ Health Study (SPATZ (2012)), n 458). Centred log ratio transformation was applied to fatty acid data. Principal component analysis was used to determine study-dependent fatty acid profiles. A general linear model was used to determine the study (or period) effect on fatty acid profiles adjusting for duration of gestation, age, education, delivery mode, smoking and pre-pregnancy BMI. Two principal components were retained (PC1 and PC2). PC1 was associated with UBCS, while PC2 was associated with SPATZ. PC1 comprised high SFA, and low MUFA, n-6 and n-3 long-chain PUFA (LCPUFA). The inverse was true for PC2. Although human milk remains a source of essential fatty acids, infants could be at risk of inadequate n-3 and n-6 LCPUFA intake through human milk. The differences in the human milk fatty acid profiles also reflect changes in maternal dietary habits in the more recent cohort, which may comprise lower intakes of dietary trans-fatty acids and SFA and higher intakes of vegetable oils.

Metaproteomic investigation to assess gut microbiota shaping in newborn mice: A combined taxonomic, functional and quantitative approach

Breastfeeding is nowadays known to be one of the most critical factors contributing to the development of an efficient immune system. In the last decade, a consistent number of pieces of evidence demonstrated the relationship between a healthy organism and its gut microbiota. However, this link is still not fully understood and requires further investigation. We recently adopted a murine model to describe the impact of either maternal milk or parental genetic background, on the composition of the gut microbial population in the first weeks of life. A metaproteomic approach to such complex environments is a big challenge that requires a strong effort in both data production and analysis, including the set-up of dedicated multitasking bioinformatics pipelines. Herein we present an LC-MS/MS based investigation to monitor mouse gut microbiota in the early life, aiming at characterizing its functions and metabolic activities together with a taxonomic description in terms of operational taxonomic units. We provided a quantitative evaluation of bacterial metaproteins, taking into account differential expression results in relation to the functional and taxonomic classification, particularly with proteins from orthologues groups. This allowed the reduction of the bias arising from the presence of a high number of shared peptides, and proteins, among different bacterial species. We also focused on host mucosal proteome and its modulation, according to different microbiota composition. SignificanceThis paper would represent a reference work for investigations on gut microbiota in early life, from both a microbiological and a functional proteomic point of view. We focused on the shaping of the mouse gut microbiota in dependence on the feeding modality, defining a reliable taxonomic description, highlighting some functional characteristics of the microbial community, and performing a first quantitative evaluation by data independent analysis in metaproteomics.

Maternal lineage of Okinawa indigenous Agu pig inferred from mitochondrial DNA control region.

ObjectiveThe Agu is the only native pig breed in Japan, which is reared in Okinawa prefecture, the southernmost region in Japan. Its origins are considered to be of Asian lineage; however, the genetic background of the Agu is still unclear. The objective of this study was to elucidate the maternal lineage of the Okinawa indigenous Agu pig with the use of the mitochondrial DNA (mtDNA) control region.MethodsThe mtDNA control regions of Agu pigs were sequenced and the phylogenetic relationship among Agu, East Asian and European pigs was investigated with the use of 78 Agu individuals.ResultsTwenty-seven polymorphic sites and five different haplotypes (type 1 to type 5) were identified within the Agu population. Phylogenetic analysis indicated that types 1 and 2 were included in East Asian lineages; however, the remaining types 3, 4, and 5 were of European lineages, which showed a gene flow from European pigs in the 20th century. Sixty-seven out of 78 Agu individuals (85.9%) possessed mtDNA haplotypes 1 and 2 of the East Asian lineage, which were identical to two haplotypes of ancient mtDNA (7,200 to 1,700 years before the present) excavated at archaeological sites in Okinawa.ConclusionThis study confirmed that the East Asian lineage is dominant in the maternal genetic background of the Agu population, supporting the hypothesis that the ancestors of the Agu pig were introduced from the Asian continent.

Noninvasively diagnosing for fetal trisomy 21 by examining heterozygous single nucleotide polymorphisms in the placental specific genes on chromosome 21

ObjectiveNoninvasive prenatal diagnosing for fetal trisomy 21 could help to avoid unnecessary amniocentesis. It is feasible to target the cell-free placental-specific mRNA in maternal plasma, thus eliminating the interference from the maternal genetic background. Study designIn this study, placental-specific genes on chromosome 21 were identified by searching the TiGER database and reviewing the published literature. These cell-free placental-specific mRNA fragments in maternal plasma were amplified and sequenced. Then, the allelic ratio of heterozygous single-nucleotide polymorphisms(SNPs) was analyzed. ResultsFour placental-specific genes (DNMT3L, KRTAP26-1, PLAC4, DSCR4) were identified. This study included 42 cases of normal pregnancies and 19 cases of trisomy 21 pregnancies. The probability density function showed that the allelic ratio of heterozygous SNPs in normal pregnancy reached a peak at 1.0, and that in the trisomy 21 pregnancy was a double-peaked curve in both 0.5 and 2.0. However, the allelic ratio of heterozygous SNPs demonstrated no statistical difference between the normal and trisomy 21 pregnancies. ConclusionFetal trisomy 21 could not be diagnosed by examining the heterozygous SNPs of cell-free placental-specific mRNA on chromosome 21. This might be because the low quantity and quality of cell-free placental-specific mRNA fragments in maternal plasma, and the limited available heterozygous SNPs on the placental-specific genes.

Different thermotolerances in invitro-produced embryos derived from different maternal and paternal genetic backgrounds.

The present study evaluated the effects of genetic backgrounds on the developmental competence and thermotolerance of bovine invitro-produced (IVP) embryos. First, Holstein (Hol) and Japanese Black (JB) oocytes were fertilized with sperm from Hol, JB and a thermotolerant breed (Brahman), and invitro development was evaluated when the embryos were exposed to heat shock on Day 2 (Day 0=day of fertilization). Sperm genetic backgrounds affected the developmental competence in controls (P<0.05). Second, the effect of sperm pre-incubation for 4h on subsequent invitro fertilization was assessed using different sperm genetic backgrounds. The pre-incubation of sperm did not decrease the embryonic development regardless of the breed of the sperm. A milder heat shock (40.0°C) effect on parthenotes (Hol and JB) and IVP embryos were evaluated. JB parthenotes showed developmental arrest after Day 4, and the rate of development to the blastocyst stage decreased by heat shock, but not in Hol parthenotes. Heat shock decreased developmental competence after cleavage of IVP embryos regardless of genetic background. The thermotolerance of IVP embryos would be controlled by both maternal and paternal factors but genetic involvement was still unclear. Further evaluation is needed to reveal the genetic contribution to thermotolerance.

Maternal genetic backgrounds contribute to the genetic susceptibility of tongue cancer patients in Hunan, central of China

Mitochondrial DNA (mtDNA) mutations played crucial roles on affecting the susceptibility to cancer. In this study, to investigate whether mitochondrial DNA mutations contributed to the genetic susceptibility of Chinese tongue cancer patients, mtDNA control regions of 105 Chinese tongue cancer patients were amplified and sequenced, the mutations were recorded by comparing with the revised Cambridge Reference Sequence (rCRS), which were attributed to certain mtDNA haplogroups based on the specific variations motif of each patients. The Miao Chinese group (a Chinese ethnic minority) from surrounding region has no essential difference with tongue cancer group, which was taken as the matched control group with principal component analysis by taking the haplogroups frequency of 105 tongue cancer individuals and 354 healthy individuals of eight groups from the similar geographic regions as input factors. This was supported by the smallest genetic distance between tongue cancer and Miao_2 groups. Further, the statistical analysis based on mtDNA variations of hypervariable sequence I (HVSI) indicated that 13 variations including 16,124, 16,148, 16,182C, 16,183C, 16,227, 16,266A, 16,249, 16,272, 16,291, 16,327, 16,335, 16,497, and 16,519 have significant differences between tongue cancer group and matched control group. Comparison of mtDNA haplogroups between tongue cancer and control groups indicated that mtDNA haplogroups C, F2*, and M10 have significant differences. It’s worth noting that 16,327 and 16,291 was the defining variation of haplogroups C and F2*, respectively. Our results suggested that mitochondrial DNA may play a crucial role for the maternal genetic susceptibility of tongue cancer patients from Hunan, central of China.

292: Maternal genetic background impacts pregnancy and neonatal outcomes in pregnancies complicated by intrauterine infection and inflammation

292: Maternal genetic background impacts pregnancy and neonatal outcomes in pregnancies complicated by intrauterine infection and inflammation

The maternal-age-associated risk of congenital heart disease is modifiable

Maternal age is a risk factor for congenital heart disease even in the absence of any chromosomal abnormality in the newborn1-7. Whether the basis of the risk resides with the mother or oocyte is unknown. The impact of maternal age on congenital heart disease can be modeled in mouse pups that harbor a mutation of the cardiac transcription factor gene Nkx2-58. Here, reciprocal ovarian transplants between young and old mothers establish a maternal basis for the age-associated risk. A high-fat diet does not accelerate the effect of maternal aging, so hyperglycemia and obesity do not simply explain the mechanism. The age-associated risk varies with the mother's strain background, making it a quantitative genetic trait. Most remarkably, voluntary exercise, whether begun by mothers at a young age or later in life, can mitigate the risk when they are older. Thus, even when the offspring carry a causal mutation, an intervention aimed at the mother can meaningfully reduce their risk of congenital heart disease.

245 EFFECTS OF Gyr (BOS TAURUS INDICUS) DONOR MITOCHONDRIAL DNA AND OVUM PICKUP ORDER ON IN VITRO EMBRYO PRODUCTION

Ovum pick (OPU) up is a technique upon which in vitro embryo production (IVP) depends. It permits donor cow maternal ancestry to be assessed by mtDNA analysis. Repetitive ablation of follicles is thought to interfere with the donor cow endocrine profile and influence embryo yield. The objective was to evaluate the effects of mtDNA and OPU order on IVP fertility traits. Gyr donors (85) were submitted to 363 OPU sessions (5 OPU sessions/donor). Donor mtDNA was extracted from leukocytes and sorted by the presence of the HindIII restriction site within the amplified region, indicative of Bos taurus taurus mtDNA (Paneto et al. 2008 Genet. Mol. Res. 7, 592). All animals in the donor pedigree were classified, and the population was divided into two groups according to their maternal genetic grouping: Bos taurus indicus and Bos taurus taurus. For statistical analyses, data from 5 OPU sessions per each donor were submitted to the mixed model procedure of SAS® (SAS Institute Inc., Cary, NC, USA), using the lowest Akaike value to determine the best covariance structure between repeated OPU session results. The model included the effect of OPU session order (1–5) and mtDNA-based maternal grouping (Bos taurus v. Bos indicus) as independent variables. Total and viable oocytes, as well as blastocyst yield per OPU session, were the dependent variables studied. The means of total and viable oocytes and blastocysts produced per donor per OPU were compared by the Tukey test, at 5% significance. The combined OPU sessions resulted in 6084 oocytes, 2537 embryos, which produced 1105 pregnancies. Mean numbers (n = 42 donors/OPU session) of total and viable oocytes between OPU sessions 1 (31.9 ± 4.6 and 19.2 ± 2.9), 2 (35.3 ± 3.5 and 21.2 ± 2.2), 3 (28.9 ± 3.7 and 19.3 ± 2.4), 4 (25.0 ± 5.2 and 18.9 ± 33), and 5 (20.5 ± 6.3 and 13.8 ± 4.0) did not differ. Mean blastocyst production after IVP between OPU sessions 1 (6.5 ± 1.4), 2 (5.15 ± 1.04), 3 (5.5 ± 1.1), 4 (5.8 ± 1.6), and 5 (5.2 ± 1.9) was similar. Mean viable oocyte number was greater (P &lt; 0.0001) for B. t. taurus (21.7 ± 1.4, n = 192 OPU sessions) compared with B. t. indicus (16.1 ± 0.9, n = 138 OPU sessions) maternal genetic groupings. However, in vitro blastocyst yields were similar (P = 0.23) between maternal genetic groupings (7.3 ± 1.6 and 6.2 ± 1.4 for B. taurus and B. indicus, respectively). In conclusion, repeated OPU sessions did not reduce oocyte and embryo yields as expected. Maternal B. taurus genetic origin was associated with higher oocyte quality, although it was not translated into higher embryo yields after in vitro culture. Results warrant further research, which may result in additional selection criteria for OPU Gyr donors considering their maternal genetic background.

Complete mtDNA genomes reveal similar penetrances of maternally inherited type 2 diabetes in two Chinese families

Previous work suggests that mitochondrial DNA (mtDNA) derived from the maternal genome has a close affinity with type 2 diabetes. This would support a familial pattern for type 2 diabetes. Thereby, we analyzed complete mtDNA genomes from two families, A and B, from Southwest China that demonstrated maternally inherited type 2 diabetes. Our data support that mtDNA lineages from families A and B belong to haplogroups A4 and D4h1, respectively. This suggests that maternally inherited type 2 diabetes with similar penetrances can arise in Chinese individuals with strikingly different maternal genetic backgrounds. Two private coding region mutations (G13759A in MT-ND5 and G15930A in tRNA-Thr) were identified in family B. Further evolutionary and phylogenetic analyses suggest that both these mutations have multiple origins and are unlikely to be disease causing.