Genetic parameters, genetic trends and correlated responses of growth traits considering maternal ability in Nelore cattle.

The growth of Nelore cattle was analysed considering the following performance parameters; the effect of the calving order of cows on the phenotypic expression of birth weight (BW), average daily gain from birth to weaning (BWG), and weaning weight (WW), the estimated genetic parameters for the traits, including the covariance components between direct and maternal genetic effects. Genetic trends and correlated responses were also obtained for the studied traits. The calving order of cows, as well as other fixed effects used to obtain the adjusted phenotypic means, were statistically significant (p < 0.001) for studied traits. Direct heritability was estimated at 0.24 ± 0.01 (BW), 0.15 ± 0.01 (BWG), and 0.18 ± 0.01 (WW), while maternal heritability was 0.06 ± 0.01 (BW), 0.12 ± 0.01 (BWG), and 0.11 ± 0.01 (WW). The correlations between direct and maternal effects within the same trait were negligible. Moderate to higher direct genetic correlations (ranging from 0.54 ± 0.04 to 0.98 ± 0.01) and maternal genetic correlations (ranging from 0.34 ± 0.09 to 0.99 ± 0.002) were estimated between the studied traits. Unlike direct genetic effects, there was no significant change in maternal genetic effects over time (p > 0.05). These results indicated the need for revising selection indexes for enhancing maternal ability. Correlated responses were generally lower compared to direct responses, except for BWG. The selection for BWG, considering the maternal genetic effect, would be more efficient to improve maternal ability of the cows for pre-weaning growth in relation to selection for WW. Our results found that direct genetic merit improves pre-weaning weight and this trait can be incorporated into the breeding goal as reflected in the WW.

Karyopherin α2 is a maternal effect gene required for early embryonic development and female fertility in mice.

The nuclear transport of proteins plays an important role in mediating the transition from egg to embryo and distinct karyopherins have been implicated in this process. Here, we studied the impact of KPNA2 deficiency on preimplantation embryo development in mice. Loss of KPNA2 results in complete arrest at the 2cell stage and embryos exhibit the inability to activate their embryonic genome as well as a severely disturbed nuclear translocation of Nucleoplasmin 2. Our findings define KPNA2 as a new maternal effect gene.

Unpredictable Chemical Diversity of Essential Oils in Cinnamomum burmanni (Lauraceae) Living Collections: Beyond Maternally Inherited Phylogenetic Relationships.

The genus Cinnamomum encompasses diverse species with various applications, particularly in traditional medicine and spice production. This study focuses on Cinnamomum burmanni, specifically on a high-D-borneol-content chemotype, known as the Meipian Tree, in Guangdong Province, South China. This research explores essential oil diversity, chemotypes, and chloroplast genomic diversity among 28 C. burmanni samples collected from botanical gardens. Essential oils were analyzed, and chemotypes classified using GC-MS and statistical methods. Plastome assembly and phylogenetic analysis were conducted to reveal genetic relationships. Results showed distinct chemotypes, including eucalyptol and borneol types, with notable variations in essential oil composition. The chloroplast genome exhibited conserved features, with phylogenetic analysis revealing three major clades. Borneol-rich individuals in clade II suggested a potential maternal inheritance pattern. However, phylogenetic signals revealed that the composition of essential oils is weakly correlated with plastome phylogeny. The study underscores the importance of botanical gardens in preserving genetic and chemical diversity, offering insights for sustainable resource utilization and selective breeding of high-yield mother plants of C. burmanni.

Maternal effects and inbreeding depression in post-translocation progeny of Campanula glomerata.

Evaluation of plant translocation success based on fitness-related quantitative traits combined with molecular markers may contribute to a finer assessment of inbreeding, selective and rescue processes, which might have long-term consequences for population dynamics and viability. We investigated fitness traits (seed germination, seedling viability, and juvenile growth and mortality) combined with 15 microsatellite loci of the first post-translocation seed progeny from two translocated populations of Campanula glomerata, an insect-pollinated, self-incompatible perennial herb. We examined whether inbreeding, heterosis through admixture, translocation site and maternal transplant seed source origin and lineage might affect seed quality and juvenile growth in controlled cultivation conditions. Flower production and seed germination of the transplants was higher in one of the two translocation sites, which might be related to differences in soil and vegetation composition and cover. Strong maternal effects related to seed source origin and lineage were found on progeny size, with the largest transplants producing the largest progeny. The differences in rosette diameter were maintained across the whole growth period measured. There was inbreeding depression (rather than heterosis) related to biparental inbreeding at the early progeny growth stage, also expressed through juvenile mortality. Our findings highlight that maternal transplant origin, especially when seed sources consisted of small, fragmented remnants, might have a selective value on fitness in the post-translocation generations. If maternal effects and inbreeding depression persist, they might affect global genetic diversity patterns in the long term. Further admixture in the next generations might buffer maternal and inbreeding effects or lead to outbreeding depression.

Combined effects of spinetoram and Microcystis aeruginosa on Daphnia pulex offspring: Maternal effects and multigenerational implications.

The increasing occurrence of harmful algal blooms (HABs) in freshwater ecosystems detrimentally affect global water environments. Zooplankton's role in controlling HABs is hindered by contaminant exposure, necessitating research into combined stressors' ecological impacts. The response of Daphnia, a freshwater keystone species, to environmental stressors can be influenced by its maternal effects. Here, we investigated the combined effects of the world-widely used insecticide spinetoram and non-toxic HABs species Microcystis aeruginosa on the life-history traits of D. pulex offspring produced from different maternal food conditions. Four maternal groups were established, with each group receiving a specific blend of C. vulgaris (Ch) and M. aeruginosa (Ma) in varying proportions: A (100% Ch), B (90% Ch + 10% Ma), C (80% Ch + 20% Ma), and D (70% Ch + 30% Ma). The offspring from the third brood were gathered, and a 21-day experiment was carried out, involving various feeding groups (AA, AD, BA, BB, CA, CC, DA, and DD). Results demonstrated that grazing on M. aeruginosa by D. pulex induced maternal effects on their offspring, with the continuous exposure group showing an enhanced tolerance to M. aeruginosa. This study also unveiled that spinetoram could interfere with the molting of D. pulex, leading to developmental retardation. The Recovery Group exhibited an intriguing phenomenon: under the influence of both concentrations of the pesticide spinetoram (0.18, 0.35 µg L-1), D. pulex produced more offspring. This might be due to a combined strategy of allocating more energy towards reproduction in response to low-quality food and a potential hormetic effect from low concentrations of spinetoram. Assessing the interplay of combined stressors across multiple generations, encompassing harmful algal blooms (HABs) and environmental pollutants, is essential for predicting population responses to evolving environmental conditions. This understanding is vital for the protection and management of aquatic environments and ecosystems.

Familial retinoblastoma: variations in clinical presentation and management based on paternal versus maternal inheritance.

BACKGROUND: Several studies have demonstrated the effect of parent-of-origin on retinoblastoma penetrance. The purpose of the current study was to assess differences in clinical presentation of paternally versus maternally inherited retinoblastoma. METHODS: The clinical records of all children with familial retinoblastoma treated on a tertiary Ocular Oncology Service between December 1975 and May 2020 were reviewed retrospectively. RESULTS: A total of 179 patients with familial retinoblastoma were included. Paternal inheritance (PI) was identified in 109 (61%) patients and maternal inheritance (MI) in 70 patients (39%). A comparison (PI vs MI) revealed PI patients were older at presentation (57.2 vs 24.4 months [P = 0.002]) with no difference in patient sex (53% females vs 57% males [P = 0.606]) or number of family members affected (3.2 vs 3.0 family members [P = 0.255]). PI patients had more advanced classification according to the International Classification of Retinoblastoma (ICRB) (group E: 31% vs 8% [P = 0.012)] and greater largest tumor in basal diameter (9.0 vs 6.2 mm [P = 0.040]) and thickness (5.6 vs 4.0 mm [P = 0.038]); they were also less likely to be located in the macula (40% vs 60% [P = 0.004]). There was no difference in tumor laterality (69% vs 64% bilaterality [P = 0.530]). PI patients required enucleation more frequently (34% vs 14% [P = 0.007]). There was no difference in need for plaque radiotherapy (P = 0.86) or chemotherapy (P = 0.85). One PI patient developed metastatic retinoblastoma, and there were no retinoblastoma-related deaths. CONCLUSIONS: Patients with paternally inherited retinoblastoma presented at an older age, with larger, more peripheral tumors and more advanced ICRB group, and were more likely to require enucleation compared to those with maternally inherited retinoblastoma.

Analysis of the maternal inheritance hypothesis of the exochorium in eggs from hybrids of Chagas disease vectors.

Morphological studies applied to the taxonomy of the Triatominae cover various structures (head, wing, thorax, genitalia, and eggs). Exochorial structures of hybrid eggs were characterized and compared with the parents, demonstrating that hybrids presented characteristics identical to the exochorial pattern observed in the females of the crosses, which resulted in the hypothesis that the pattern of triatomine eggs is possibly a characteristic inherited from females. Thus, we characterized the exochorium of the eggs of several triatomine hybrids and compared them with the parents, to assess the pattern of segregation and test the hypothesis of maternal inheritance. Hybrids were obtained in at least one direction from all crosses. The analysis of the exochorium of the eggs of the hybrids showed different patterns of segregation: "exclusively paternal", "predominantly maternal", "predominantly paternal", "mutual", and "differential". Curiously, none of the hybrids evaluated presented characteristics that segregated exclusively from the female parental species. Thus, we demonstrate that the hypothesis of maternal inheritance of the exochorium pattern of eggs is not valid and we emphasize the importance of alternative/combined tools (such as integrative taxonomy) for the correct identification of these insect vectors (mainly in view of possible natural hybridization events due to climate and environmental changes).

Incubation as a driver of maternal effects: Temperature influences levels of yolk maternally derived 5α-dihydrotestosterone.

In birds, maternal hormones deposited into eggs in response to environmental stimuli can impact offspring phenotype. Although less studied, environmental conditions can also influence females' incubation behavior, which might play a role in regulating embryo exposure to maternal hormones through changes in incubation temperature that affect the activity of the enzymes responsible for converting testosterone (T) to 5α-dihydrotestosterone (DHT) or estradiol. Here, we tested the hypothesis that the initial T content of the yolk and incubation temperature determine exposure to T metabolites during early embryo development. In the Japanese quail (Coturnix japonica), we experimentally manipulated yolk T and incubation temperature (38° C versus 36° C) and analyzed DHT and estradiol titers on day four of incubation. We found that eggs with experimentally increased T and those incubated at 36° C showed higher DHT concentration in egg yolk (with no synergistic effect of the two treatments). Estradiol titers were not affected by T manipulation or incubation temperature. Our study suggests that incubation temperature influences DHT titers and may act as an understudied source of maternal influence on offspring phenotype.

A new family with a case of severe early-onset muscle fatigue and a peculiar maternally inherited painful swelling in chewing muscles associated with homoplasmic m.15992A>T mutation in mitochondrial tRNAPro.

A 16-year-old boy was evaluated for a history of exercise-induced fatigability associated with nausea even after minimal effort, lower limbs muscle hypotrophy, and swelling of the masseter muscles after chewing. Laboratory tests were remarkable for hyperlactatemia and metabolic acidosis after short physical activity. The muscle biopsy showed non-specific mitochondrial alterations and an increase in intrafibral lipids. Biochemical analysis showed reduced activity of the respiratory chain complexes. Mitochondrial DNA sequencing revealed the presence of a homoplasmic variant m.15992A>T in the MT-TP gene, coding for the mt-tRNAPro in the patient, in his mother and in his brother. Pathogenic or likely pathogenic variants in MT-TP gene are rare. They are responsible for different clinical presentation, almost ever involving the muscle tissue. We report the first family with exercise-induced muscle weakness and swelling of the chewing muscles due to m.15992A>T variant in absence of J1c10 haplogroup, confirming its pathogenicity.

Direct, carryover, and maternal effects of ocean acidification on snow crab embryos and larvae.

Ocean acidification, a decrease in ocean pH with increasing anthropogenic CO2 concentrations, is expected to affect many marine animals. To examine the effects of decreased pH on snow crab (Chionoecetes opilio), a commercial species in Alaska, we reared ovigerous females in one of three treatments: Ambient pH (~8.1), pH 7.8, and pH 7.5, through two annual reproductive cycles. Morphometric changes during development and hatching success were measured for embryos both years and calcification was measured for the adult females at the end of the 2-year experiment. Embryos and larvae analyzed in year one were from oocytes developed, fertilized, and extruded in situ, whereas embryos and larvae in year two were from oocytes developed, fertilized, and extruded under acidified conditions in the laboratory. In both years, larvae were exposed to the same pH treatments in a fully crossed experimental design. Starvation-survival, morphology, condition, and calcium/magnesium content were assessed for larvae. Embryo morphology during development, hatching success, and fecundity were unaffected by pH during both years. Percent calcium in adult females' carapaces did not differ among treatments at the end of the experiment. In the first year, starvation-survival of larvae reared at Ambient pH but hatched from embryos reared at reduced pH was lowered; however, the negative effect was eliminated when the larvae were reared at reduced pH. In the second year, there was no direct effect of either embryo or larval pH treatment, but larvae reared as embryos at reduced pH survived longer if reared at reduced pH. Treatment either did not affect other measured larval parameters, or effect sizes were small. The results from this two-year study suggest that snow crabs are well adapted to projected ocean pH levels within the next two centuries, although other life-history stages still need to be examined for sensitivity and potential interactive effects with increasing temperatures should be investigated.

Maternally inherited siRNAs initiate piRNA cluster formation.

PIWI-interacting RNAs (piRNAs) guide transposable element repression in animal germ lines. In Drosophila, piRNAs are produced from heterochromatic loci, called piRNA clusters, which act as information repositories about genome invaders. piRNA generation by dual-strand clusters depends on the chromatin-bound Rhino-Deadlock-Cutoff (RDC) complex, which is deposited on clusters guided by piRNAs, forming a positive feedback loop in which piRNAs promote their own biogenesis. However, how piRNA clusters are formed before cognate piRNAs are present remains unknown. Here, we report spontaneous de novo piRNA cluster formation from repetitive transgenic sequences. Cluster formation occurs over several generations and requires continuous trans-generational maternal transmission of small RNAs. We discovered that maternally supplied small interfering RNAs (siRNAs) trigger de novo cluster activation in progeny. In contrast, siRNAs are dispensable for cluster function after its establishment. These results reveal an unexpected interplay between the siRNA and piRNA pathways and suggest a mechanism for de novo piRNA cluster formation triggered by siRNAs.

Rapid decline of prenatal maternal effects with age is independent of postnatal environment in a precocial bird.

Maternal effects are an important source of phenotypic variation with potentially large fitness consequences, but how their importance varies with the quality of the environment across an individual's ontogeny is poorly understood. We bred Japanese quail (Coturnix japonica) of known pedigree and experimentally manipulated the quality of the offspring diet, to estimate the importance of prenatal maternal effects in shaping variation in body mass from hatching to adulthood. Maternal genetic effects on body mass at hatching were strong, and largely caused by variation in egg mass, but their importance rapidly declined with age. Whereas there was a large effect of diet on growth, this did not affect the decline of maternal effects variance. The importance of additive genetic and residual variance increased with age, with the latter being considerably larger in the poor diet treatment. Hence, we found no evidence for prenatal maternal effect by postnatal environment interactions and that prenatal maternal effects are rapidly replaced by direct additive genetic and residual effects when offspring start to develop outside the egg. Thereby these results shed new light on the dynamics of the role of maternal versus offspring genes across ontogeny and environments.

The mutational analysis of mitochondrial DNA in maternal inheritance of polycystic ovarian syndrome.

Introduction: Polycystic Ovarian Syndrome (PCOS) is a globally prevalent condition that leads to infertility in women. While environmental factors contribute to PCOS, maternal genetics also play a significant role. Currently, there is no definitive test for identifying predisposition to PCOS. Hence, our objective is to discover novel maternal genetic risk factors for PCOS by investigating the genomes of patients from Pakistan. Methods: We utilized Next-Generation Sequencing (NGS) to sequence the complete mitochondrial DNA of three PCOS patients. Subsequently, we employed MitoTIP (Mitochondrial tRNA Informatics Predictor) and PON-mt-tRNA tools to identify variations in the mitochondrial DNA. Our analysis focused on the genes MT-RNR1, MT-RNR2, MT-ATP6, MT-TL2, and MT-CYTB, which displayed common variations in all three genomes. Additionally, we observed individual variations. The D-loop region exhibited the highest frequency of mutations, followed by the non-coding regions of RNR1 and RNR2 genes. Moreover, we detected frameshift mutations in the mitochondrially encoded NADH Dehydrogenase 2 (MT-ND2) and mitochondrially encoded NADH Dehydrogenase 5 (ND5) genes within individual genomes. Results: Our analysis unveiled six regions with common variations in the mitochondrial DNA of all three PCOS patients. Notably, the MT-RNR1, MT-RNR2, MT-ATP6, MT-TL2, and MT-CYTB genes exhibited these variations. Additionally, we identified individual variations in the mitochondrial DNA. The D-loop region displayed the highest mutation frequency, followed by the non-coding regions of RNR1 and RNR2 genes. Furthermore, frameshift mutations were detected in the MT-ND2 and ND5 genes within individual genomes. Conclusion: Through our study, we have identified variations in mitochondrial DNA that may be associated with the development of PCOS and have the potential to serve as predisposition tests. Our findings highlight the presence of novel mutations in the MT-RNR1, MT-RNR2, MT-ATP6, MT-TL2, and MT-CYTB genes, as well as frameshift mutations in the MT-ND2 and ND5 genes. Pathogenicity analysis indicated that most variants were likely to result in benign cysts. However, the frameshift mutations in the ND2 gene were associated with a high risk of complications and pathogenicity in PCOS. This is the first report identifying these mutations and their association with PCOS, contributing to our understanding of the genetic factors underlying the condition.

Molecular basis for maternal inheritance of human mitochondrial DNA.

Uniparental inheritance of mitochondrial DNA (mtDNA) is an evolutionary trait found in nearly all eukaryotes. In many species, including humans, the sperm mitochondria are introduced to the oocyte during fertilization1,2. The mechanisms hypothesized to prevent paternal mtDNA transmission include ubiquitination of the sperm mitochondria and mitophagy3,4. However, the causative mechanisms of paternal mtDNA elimination have not been defined5,6. We found that mitochondria in human spermatozoa are devoid of intact mtDNA and lack mitochondrial transcription factor A (TFAM)-the major nucleoid protein required to protect, maintain and transcribe mtDNA. During spermatogenesis, sperm cells express an isoform of TFAM, which retains the mitochondrial presequence, ordinarily removed upon mitochondrial import. Phosphorylation of this presequence prevents mitochondrial import and directs TFAM to the spermatozoon nucleus. TFAM relocalization from the mitochondria of spermatogonia to the spermatozoa nucleus directly correlates with the elimination of mtDNA, thereby explaining maternal inheritance in this species.

Imeglimin-mediated glycemic control in maternally inherited deafness and diabetes.

Mitochondrial dysfunction causes maternally inherited deafness and diabetes (MIDD). Herein, we report improved glycemic control in a 47-year-old Japanese woman with MIDD using imeglimin without major adverse effects. Biochemical tests and metabolome analysis were performed before and after imeglimin administration. Blood glucose level fluctuations were determined. Sulfonylureas, dipeptidyl peptidase-4 inhibitors (DPP4is), and sodium glucose transporter-2 inhibitors (SGLT2i) were administered to evaluate the efficacy of their combination with imeglimin. Imeglimin decreased the HbA1c and ammonia levels and increased the time-in-range, C-peptide reactivity, and glucagon level. Elevated citrulline and histamine levels were decreased by imeglimin. The hypoglycemic effect was not enhanced by imeglimin when combined with sulfonylurea or DPP4i, but the blood glucose level was improved when combined with SGLT2i. Imeglimin improved glucose concentration-dependent insulin secretion and maximized the insulin secretory capacity by improving mitochondrial function and glutamine metabolism and urea circuit abnormalities by promoting glucagon secretion. Imeglimin could improve glycemic control in MIDD.

Evaluation of reciprocal F1 crosses of Fayoumi with two exotic chicken breeds 1: additive and non-additive effects on egg production traits.

The present study estimates additive and non-additive effects on egg production traits in genotypes generated through pure mating and reciprocal crossing of Fayoumi (FM) with Koekoek (KK) and White Leghorn (WL). Age at first egg (AFE) and body weight at first egg (BWAFE) were determined when the first bird in the pen laid its first egg, and egg weight at first egg (EWAFE) was the average weight of eggs laid consecutively during the first 10 days. Egg number (EN) and egg weight (EW) were recorded daily from AFE to 40 weeks of age. Egg mass (EM) was the product of EN and EW. EN of hens initially housed and hens alive during the experiment were used to calculate hen-housed egg production (HHEP) and hen-day egg production (HDEP), respectively. All the traits showed statistically significant differences among the genotypes. The results revealed the importance of additive and non-additive effects, where purebred effect (PE), general combining ability (GCA), maternal effect (ME), specific combining ability (SCA), and residual reciprocal effect (RRE) significantly affected most of the traits. The KK and WL had a higher PE, and GCA was highest in KK, with FM and WL showing a higher ME. The FM x WL had higher SCA and RRE. The KK x FM and FM x WL outperformed their main and reciprocal crosses, respectively, and purebred contemporaries. Therefore, a synthetic breeding program involving KK as a sire and FM, WL, FM x WL, and KK x FM as a dam would be feasible.

Rapid and biased evolution of canalization during adaptive divergence revealed by dominance in gene expression variability during Arctic charr early development.

Adaptive evolution may be influenced by canalization, the buffering of developmental processes from environmental and genetic perturbations, but how this occurs is poorly understood. Here, we explore how gene expression variability evolves in diverging and hybridizing populations, by focusing on the Arctic charr (Salvelinus alpinus) of Thingvallavatn, a classic case of divergence between feeding habitats. We report distinct profiles of gene expression variance for both coding RNAs and microRNAs between the offspring of two contrasting morphs (benthic/limnetic) and their hybrids reared in common conditions and sampled at two key points of cranial development. Gene expression variance in the hybrids is substantially affected by maternal effects, and many genes show biased expression variance toward the limnetic morph. This suggests that canalization, as inferred by gene expression variance, can rapidly diverge in sympatry through multiple gene pathways, which are associated with dominance patterns possibly biasing evolutionary trajectories and mitigating the effects of hybridization on adaptive evolution.

Genetic Counseling and Prenatal Diagnosis of a Maternally Inherited 15q11.2 Microduplication.

Unbalanced chromosome abnormalities (UBCA) are large genomic region variations that often result in minimal clinical effects. Copy number variants (CNVs), such as microdeletions and microduplications in 15q11.2, have been linked to various health issues, making prenatal diagnosis and genetic counselling challenging. Microdeletions and microduplications in the genomic region 15q11.2 are associated with congenital heart defects, autism, schizophrenia, epilepsy, mental retardation and developmental delay. The literature on this microduplication is confusing and extensive, which is a great difficulty for prenatal diagnosis and genetic counselling. A 35-year-old female undergoing amniocentesis at Week 19 due to advanced maternal age revealed a normal 46,XX karyotype through G-banding analysis. However, Chromosomal microarray analysis (CMA) on the same amniocytes detected a 550-Kb maternally inherited chromosomal microduplication in 15q11.2. An integrated approach combining karyotype analysis, CMA, genetic counseling, and prenatal ultrasound is crucial for the accurate prenatal diagnosis of UBCAs and CNVs.

Prenatal Diagnosis and Genetic Counseling of a Maternally Inherited Chromosome 15q11.2q13.1 Duplication in a Chinese Family.

Background: Maternally inherited chromosomal duplications in the region of 15q11.2q13.1 have been associated with neurodevelopmental disorders and other clinical manifestations. Prenatal diagnosis of such duplications is crucial for providing accurate genetic counseling and guiding clinical management decisions. Objective: This study aims to present the prenatal diagnosis and genetic counseling of a maternally inherited 15q11.2q13.1 duplication. Case Presentation: A 38-year-old gravida 1, para 0 woman underwent amniocentesis at 16 weeks of gestation due to advanced maternal age. Karyotype analysis was performed on cultured amniocytes, and chromosomal microarray analysis (CMA) was conducted on uncultured amniocytes. Results: The karyotype analysis of the cultured amniocytes revealed a normal karyotype of 46, XX. CMA identified a 4.21 Mb maternally inherited chromosomal duplication in the region of 15q11.2q13.1 (arr[GRCh37]15q11.2q13.1(23,894,550_28,107,154)x3). Conclusions: Copy number variants (CNVs) and unbalanced chromosomal abnormalities (UBCA) identified in prenatal cases require careful consideration and accurate interpretation to determine their potential harm or harmlessness compared to the norm. The combination of prenatal ultrasound, karyotype analysis, CMA, and genetic counseling proves helpful in the prenatal diagnosis of CNVs and UBCA.