Identity-by-state-based haplotyping expands the application of comprehensive preimplantation genetic testing

STUDY QUESTION Is it possible to haplotype parents using parental siblings to leverage preimplantation genetic testing (PGT) for monogenic diseases and aneuploidy (comprehensive PGT) by genome-wide haplotyping? SUMMARY ANSWER We imputed identity-by-state (IBS) sharing of parental siblings to phase parental genotypes. WHAT IS KNOWN ALREADY Genome-wide haplotyping of preimplantation embryos is being implemented as a generic approach for genetic diagnosis of inherited single-gene disorders. To enable the phasing of genotypes into haplotypes, genotyping the direct family members of the prospective parent carrying the mutation is required. Current approaches require genotypes of either (i) both or one of the parents of the affected prospective parent or (ii) an affected or an unaffected child of the couple. However, this approach cannot be used when parents or children are not attainable, prompting an investigation into alternative phasing options. STUDY DESIGN, SIZE, DURATION This is a retrospective validation study, which applied IBS-based phasing of parental haplotypes in 56 embryos derived from 12 PGT families. Genome-wide haplotypes and copy number profiles generated for each embryo using the new phasing approach were compared with the reference PGT method to evaluate the diagnostic concordance. PARTICIPANTS/MATERIALS, SETTING, METHODS This study included 12 couples with a known hereditary genetic disorder, participating in the comprehensive PGT program and with at least one parental sibling available (e.g. brother and/or sister). Genotyping data from both prospective parents and the parental sibling(s) were used to perform IBS-based phasing and to trace the disease-associated alleles. The outcome of the IBS-based PGT was compared with the results of the clinically implemented reference haplotyping-based PGT method. MAIN RESULTS AND THE ROLE OF CHANCE IBS-based haplotyping was performed for 12 PGT families. In accordance with the theoretical prediction of allele sharing between sibling pairs, 6 out of 12 (50%) couples or 23 out of 56 embryos could be phased using parental siblings. In families where phasing was possible, haplotype calling in the locus of interest was 100% concordant between the reference PGT method and IBS-based approach using parental siblings. LARGE SCALE DATA N/A LIMITATIONS, REASONS FOR CAUTION Phasing of parental haplotypes will only be possible when the disease locus lies in an informative region (categorized as IBS1). Phasing prospective parents using relatives with reduced genetic relatedness as a reference (e.g. siblings) decreases the size and the occurrence of informative IBS1 regions, necessary for haplotype calling. By including more than one extended family member, the chance of obtaining IBS1 coverage in the interrogated locus can be increased. A pre-PGT work-up can define whether the carrier couple could benefit from this approach. WIDER IMPLICATIONS OF THE FINDINGS Phasing by relatives extends the potential of comprehensive PGT, since it allows the inclusion of couples who do not have access to the standard phasing references, such as parents or offspring. STUDY FUNDING/COMPETING INTEREST(S) The study was funded by the KU Leuven grant (C14/18/092), Research Foundation Flanders (FWO; GA09311N), Horizon 2020 innovation programme (WIDENLIFE, 692065) and Agilent Technologies. J.R.V., T.V. and M.Z.E. are co-inventors of a patent ZL910050-PCT/EP2011/060211-WO/2011/157846 ‘Methods for haplotyping single-cells’ and ZL913096-PCT/EP2014/068315-WO/2015/028576 ‘Haplotyping and copy number typing using polymorphic variant allelic frequencies’ licensed to Agilent Technologies. The other authors have no conflict of interest to declare.

Reproductive Choice, in Context: Avoiding Excess and Deficiency?

This chapter on prenatal diagnosis explores the obligations on prospective parents to act morally. Specifically, the chapter explores the highly contextual and variable nature of reproductive decision making when looking at (and criticizing) parental choice with respect to prenatal testing and selective termination. The chapter engages both with those critics who argue that disability should not be grounds for selective termination of pregnancy, and those critics who argue that not only testing for significant medical conditions but also wider testing for non-medical traits might be permissible or useful. It is argued that decisions around prenatal diagnosis are private, difficult, and entail the balancing of different concerns around abortion, disability, and the good life. The chapter then explores the usefulness of the Aristotelian concepts of excess and deficiency, as a guide to navigating our way through these difficult decisions. The idea is considered that too much selection and too little selection might both potentially represent a failure to act as a virtuous prospective parent. The chapter concludes by exploring the value of seeking the Aristotelian “mean” between those concerns.

Rekayasa Rematurasi Ikan Koki Oranda (Carassius sp.) Menggunakan Hormon Oodev Pada Dosis Yang Berbeda

Oranda chef fish is a type of goldfish that has a round body with a small head and a broad tail. This fish comes from mainland china, but in Indonesia has long been able to be cultivated. The prospect of maintaining ori chef fish is quite promising because for marketing in addition to the target in the country is also a type of fish in the export and the price is quite high. Oranda Chef Fish has some favorable properties to be cultivated for example the relatively high price of spawning cycle is relatively shorter. The purpose of the other researchers Knowing how to accelerate the maturity of the gonad chef oranda using hormones Oodev with different doses. Know the effect of Oodev hormone on remediation of ori chef fish. Know the dosage of OODev hormone effective for remandasi fish chef oranda This study used an experimental method with Completely Randomized Design (RAL) consisting of 4 treatments in which the first treatment of prospective parent who was not given Oodev hormone or as control, treatment of the two candidate mothers given a dose of 0.5 mL / kg hormone, treatment of the three prospective mothers With a dose of 1 mL / kg and the last treatment where the prospective parent with a dose of 1.5 mL / kg. Each treatment was repeated 3 times each. With 8 test parameters namely; Index gonad maturity, histology gonad, fekuenditas, egg diameter, degree of egg fertilization, degree of egg penetration, larval larva and water quality. And using ANOVA Statistic Analysis data analysis tool. Based on the results of the research of all parameters Test that the dose of 1 mL / kg is the dominant dose and most effective for maturity of the parent candidate gonad and larval life rate.

Expectations of Male and Female Adoptive Parents of Different Marital Status and Sexual Orientation

Adults in the U.S. (undergraduate college students and adults recruited online) read vignettes about a fictional individual seeking to adopt an infant. Based on random assignment, participants read versions in which the prospective adoptive parent described was either an implied male or female and single, married to someone of the opposite sex, or married to someone of the same sex. After reading the vignettes, participants rated their expectations of the prospective parent’s ability to parent and their perceptions of the prospective parent’s personal characteristics. Female participants reported significantly (p < .05) higher expectations of general ability to parent and perceived higher responsibility, greater likeability, and less selfishness. Both sexes endorsed significantly lower anticipation of ability to parent and less responsibility when the prospective parent was designated as single or in a same-sex marriage. Same-sex prospective parents were additionally rated as significantly higher in immorality. Prospective fathers were rated as less likeable than prospective mothers and participants approved less of their plan to adopt. The authors discuss findings as relevant to bias favoring traditional families headed by a man and a woman with the wife taking the lead in the transition to parenthood.

Abstract 9747: Truth in Advertising: Are We Providing Consumers With the Proper Information to Participate in Decision Making About Hypoplastic Left Heart Therapies?

Introduction: Consumer Health Informatics has become an integral part of healthcare in 2015. The purpose of this survey study is to examine the information available on the internet to a parent(s) of a fetus diagnosed in utero with hypoplastic left heart disease (HLHD) and compare those to scientific, peer reviewed published data. Specifically, is the the provider data complete enough for prospective parent(s) to make a rational decision as to whether to proceed with a 3 stage repair or choose another option. Hypothesis: The formally untested hypothesis is that there is a signifcant "gap" between what is actually known to providers and what is presented to prospective parent(s)on provider websites. Methods: Using the list of the top 10 rated Pediatric Cardiovascular programs as ranked by the U.S. News World Report (USNWR) we collected the published information with respect to: # cases of HLHD operated on for Stage 1 Norwood at the hospital/program in question, Stage 2 Glenn shunt and Stage 3 Fontan; mortality at each stage ; interstage mortality ; mortality data for patients completing all 3 stages ; neurodevelopemntal outcomes and other morbidities. For comparison, we used published data on outcomes of HLHD surgery and follow-up from the Society for Thoracic Surgery as it encompasses the largest collection of datasets from many U.S. programs. We compared the STS data set to the publsihed information from the websites.. Results: Websites did not present the statistical data presented by the STS. In addition, no website listed the exact incidence of their interstage mortality, neurodevelopemntal outcomes nor morbidities at their site. Conclusions: 1. Information published on websites of the top 10 USNWR programs provide information that tell only part of the story of outcomes for HLHD. 2. Critical pieces of information such as interstage mortality and significant morbidities, are not reported. 3.We must reasses the amount and type of data presented on hospital/program websites