Joe Leigh Simpson

Joe Leigh Simpson
Florida International University | FIU · Reseach and Global Programs

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601
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Publications

Publications (601)
Article
Chromosome testing strategies, such as PGT-A, are designed to improve an IVF embryo transfer outcome by avoiding the unwitting selection of aneuploid embryos as occurs in morphology-based approaches. Newer testing technologies have revealed that some embryos may appear to have intermediate whole chromosome (or parts of a chromosome termed segmental...
Chapter
Hypogonadotropic and hypergonadotropic forms of hypogonadism exist. In the hypogonadotropic phenotype, functional etiology originates from GnRH neurons in the hypothalamus unable to permit follicle-stimulating hormone (FSH) and luteinizing hormone to stimulate ovaries. Kallmann syndrome is canonical, characterized by anosmia and also somatic anomal...
Chapter
Preimplantation genetic testing for monogenic disorders (PGT-M) is now an established clinical procedure performed for some indications that have never been considered for prenatal diagnosis, such as common late-onset disorders or preimplantation HLA typing. This chapter presents classification of major PGT-M indications, with required standards an...
Chapter
Because PGT is based on genetic analysis of a single or few cells, PGT accuracy depends heavily on limitations of single-cell DNA analysis – potential cause of misdiagnosis. So the emphasis of this chapter is on the application and adjustment of special protocols to ensure avoiding misdiagnosis. This became even more important with the application...
Chapter
Thirty-year experience indicates that PGT is safe, despite the applied invasive embryo biopsy procedure that may in future be replaced by noninvasive methodologies. No difference in anomaly rates was observed in PGT follow-up compared to general population prevalence. Extremely high accuracy of up to 99.7% was revealed in the authors’ experience of...
Chapter
This chapter focuses on mechanism and origin of aneuploidies and structural rearrangements, contributing to their PGT strategies. This is based on the author’s 30 years PGT experience, from polar body testing and FISH analysis to embryos biopsy, involving removal of 5–10 blastocyst cells, analyzed initially by array CGH, and then by next-generation...
Chapter
Although dramatic progress has been made in corrective gene therapy in recent years, prevention of genetic disorders remains the main approach. Primary preventive measures are ideally applied at the community level through prospective carrier screening for common conditions specific for each ethnic group or currently through expanding carrier scree...
Chapter
Preimplantation genetic testing (PGT) is now an established clinical option in reproductive medicine. One of the main components of PGT is obtaining biopsy material from oocytes and embryos, which may be obtained from three major sources: (1) matured oocytes from which the first and second polar body (PB1 and PB2) are removed; (2) eight-cell cleava...
Chapter
The most ethically acceptable preventive approaches are those that involve primary prevention, which is better tolerated by the society than secondary preventive measures involving pregnancy termination. The example of paradigmatic primary preventive measure is population-based folic acid containing multivitamins fortification of the major foodstuf...
Chapter
Preimplantation HLA typing (PGT-HLA) provides patients with important option not only to avoid an inherited risk but also to establish pregnancy with an exact HLA match to benefit the affected family member. So HLA typing is now an established PGT indication, to achieve stem cell transplantation treatment of affected siblings in need for compatible...
Book
Fully revised and updated with the most current information, the third edition of this practical clinical text covers all aspects of the rapidly advancing field of preimplantation genetic testing (PGT). Although PGT has become an established procedure for genetics and assisted reproduction practices over the last decade, its wider application has o...
Article
Disorders of genetic etiology exist in 2%-3% of live-born infants. Identifying couples with increased susceptibility for offspring with anomalies or genetic disorders is increasingly effective as a result of molecular advances. Preimplantation genetic testing (PGT) with the use of trophectoderm biopsy, 24-chromosome testing, and molecular testing h...
Article
One of important problems in the health care application of technological developments in genomics is the availability of prospective identification of those at need for these technologies. The development and implementation of prospective carrier screening programs in the last few years is expected to increase the uptake of PGT-M. But most of coup...
Chapter
Preimplantation genetic diagnosis (PGD) can be considered the earliest form of prenatal testing. It was first used in humans over 26 years ago. At its inception, PGD could only be performed for a limited number of genetic disorders. Technological advances in molecular biology and cytogenomics have been utilized in the field of PGD to greatly expand...
Chapter
Prenatal diagnosis serves as a complementary and increasingly essential tool in providing anticipatory guidance and genetic counseling for disease risk of inherited disorders, and is often requested by families with an affected proband. Fortunately, the use of prenatal diagnosis and fetal rescue therapy has become increasingly popular for disorders...
Article
Couples at risk for autosomal recessive congenital adrenal hyperplasia often request anticipatory guidance and genetic counseling. Initially, hormones in amniotic fluid were measured to distinguish affected female fetuses from unaffected fetuses. With the molecular era, more-targeted approaches became possible. Prenatal genetic diagnosis via amnioc...
Article
Full-text available
The original version of the Data Descriptor contained errors in the author list and affiliations. Rita Leite's first name was misspelled as "Rite" and affiliations 4 and 5 were incorrectly swapped. In addition, members of the March of Dimes Prematurity Research Center consortium were not listed in the agreed positions within the author list. These...
Article
Full-text available
Preterm birth, or the delivery of an infant prior to 37 weeks of gestation, is a significant cause of infant morbidity and mortality. In the last decade, the advent and continued development of molecular profiling technologies has enabled researchers to generate vast amount of ‘omics’ data, which together with integrative computational approaches,...
Article
Full-text available
Preterm birth is the most common single cause of perinatal and infant mortality, affecting 15 million infants worldwide each year with global rates increasing. Understanding of risk factors remains poor, and preventive interventions have only limited benefit. Large differences exist in preterm birth rates across high income countries. We hypothesiz...
Data
This file contains information on data access, ethical approvals, gestational age methodology, and variable definitions. It also includes the formulas and data sources used for the cross-country comparison as well as six supplementary figures and five supplementary tables. (DOCX)
Article
Corresponding Author: Myron Genel, MD, Yale Child Health Research Center, Department of Pediatrics, Yale University School of Medicine, PO Box 208081, New Haven, CT 06520-8081 (myron.genel@yale.edu). Published Online: August 4, 2016. doi:10.1001/jama.2016.11850. Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Fo...
Article
Prenatal treatment of congenital adrenal hyperplasia (CAH) has long involved prenatal treatment with dexamethasone, administered to the pregnant woman to prevent genital masculinization of an affected female fetus. Although it is unnecessary to treat unaffected or affected males because their genital development would not be disturbed, there has on...
Article
Full-text available
Primary ovarian insufficiency (POI) is characterized by marked heterogeneity, but with a significant genetic contribution. Identifying exact causative genes has been challenging, with many discoveries not replicated. It is timely to take stock of the field, outlining the progress made, framing the controversies and anticipating future directions in...
Article
Full-text available
Genomes and by extension chromosome territories (CTs) in a variety of organisms exhibit nonrandom organization within interphase nuclei. CTs are susceptible to movement upon induction by a variety of stimuli, including: cell differentiation, growth factors, genotoxic agents, proliferating status, and stimulants that induce novel transcription profi...
Article
Full-text available
Premature ovarian failure (POF) is a rare, heterogeneous disorder characterized by cessation of menstruation occurring before the age of 40 years. Genetic etiology is responsible for perhaps 25% of cases, but most cases are sporadic and unexplained. In this study, through whole exome sequencing in a non-consanguineous family having four affected me...
Article
Full-text available
Prenatal screening and diagnosis is currently focused on the development of a noninvasive prenatal diagnostic test capable of detecting abnormalities similar to those attainable with an invasive test. One contender is cell-free fetal DNA circulating in maternal plasma and the other is intact fetal cells either from the maternal blood or the cervix....
Article
Full-text available
The higher-order organization of chromatin is well-established, with chromosomes occupying distinct positions within the interphase nucleus. Chromatin is susceptible to, and constantly assaulted by both endogenous and exogenous threats. However, the effects of DNA damage on the spatial topology of chromosomes are hitherto, poorly understood. This s...
Article
To investigate the association between human empty spiracles homeobox 2 gene (EMX2) and incomplete müllerian fusion (IMF). Case-control study. University-based hospital. Cohort of 517 clinically well-characterized IMF cases and 563 control women. None. In cases and control women, direct sequencing of EMX2 exons and further functional studies; for f...
Chapter
Preimplantation genetic diagnosis (PGD) can be performed for any single-gene disorder whose chromosomal location is known. More than 300 different single-gene conditions have been tested for, and worldwide testing has been performed in over 12,000 in vitro fertilization (IVF) cycles for this indication. Accuracy is high and embryo biopsy seems safe...
Article
To investigate whether gene variants of SOHLH1 exist in Chinese and Serbian patients with primary ovarian insufficiency (POI). Case-control genetic study. University hospitals. A total of 364 Han Chinese and 197 Serbian women with nonsyndromic POI and ethnically matched controls. None. SOHLH1 gene sequencing. We found 10 novel heterozygous variants...
Article
Full-text available
Background In premature ovarian failure (POF), cessation of menstruation occurs before the expected age of menopause. Approximately 1% of women are affected. FMR1 premutation was reported to be responsible for up to 3.3%–6.7% of sporadic POF and 13% of familial cases in Caucasians, while the data was absent in Chinese population. Therefore, the imp...
Article
Assisted reproductive technologies (ART) using in-vitro fertilization (IVF) account for ∼1% of births in the USA and as much as 3–4% in Europe or Australia. Initially studies involved infants prospectively examined in an early cohort of US births, with salutary results. Later studies began to show the frequency of birth defects to be increased. In...
Article
Genetic factors are pivotal in reproductive development and subsequent reproductive processes. If disturbed, infertility can occur. In the female, genetic factors affecting the ovary and the uterus are not uncommon causes of infertility. Terminal deletions on the X long arm and X short arm and X chromosomal mosaicism have long been accepted as caus...
Article
Objective To determine whether variants in the SOHLH2 gene contribute to human premature ovarian failure (POF) in different ethnicities. Design Case-control genetic study. Setting University hospitals. Patient(s) Chinese (364 cases) and Serbian (197 cases) women with nonsyndromic POF and ethnically matched controls. Intervention(s) None. Main...
Article
Objectives: Current US healthcare delivery systems do not adequately address healthcare demands. Physicians are integral but rarely emphasize prevention as a primary tool to change health outcomes. Home visitation is an effective method for changing health outcomes in some populations. The Florida International University Herbert Wertheim College...
Article
Genetic control of male sex differentiation involves sex-determining region Y (SRY) (Y chromosome) derepressing an autosomal region to allow SOX9 (17q24.1) expression. In the absence of SRY and SOX9, ovaries develop under influence of FOXL2 (3q21). Many perturbations resulting in disorders of sex development (DSD), including sex-reversed males (46,...
Article
Full-text available
The etiology of most premature ovarian failure (POF) cases is usually elusive. Although genetic causes clearly exist and a likely susceptible region of 8q22.3 has been discovered, no predominant explanation exists for POF. More recently, evidences have indicated that mutations in NR5A1 gene could be causative for POF. We therefore screened for muta...
Article
Full-text available
To identify whether variants found in a large Han Chinese cohort - 8q22.3 SNPs rs3847153 and rs3108910; and one SNP each in HK3 (rs2278493), ESR1 (rs2234693) and BRSK1 (rs12611091) - are associated with premature ovarian failure (POF) in a different ethnic group (Serbian). Case-control genetic association study in 197 Serbian POF cases and 552 matc...
Article
In the late 1980s chorionic villus sampling (CVS) became available, permitting first trimester diagnosis. Now, maternal administration of dexamethasone to prevent genital virilization can be restricted to pregnancies with affected female fetuses earlier in gestation. If the fetus were male, affected with CAH or not, treatment could cease, and would...
Article
Every year, 1·1 million babies die from prematurity, and many survivors are disabled. Worldwide, 15 million babies are born preterm (<37 weeks' gestation), with two decades of increasing rates in almost all countries with reliable data. The understanding of drivers and potential benefit of preventive interventions for preterm births is poor. We exa...
Article
Biomarkers can be employed for screening for fetal genetic disorders, identifying individuals at sufficiently high risk for a confirmatory invasive procedure. In this article we discuss prenatal genetic aneuploidy screening. Maternal serum analytes and ultrasound have long been routinely offered, providing detection rates of 80% to 93% for trisomy...
Article
In this contribution, we consider detection of 47,XXY by a variety of available methods. These include traditional invasive procedures, screening with maternal serum analytes and fetal ultrasound, and most recently cell-free fetal DNA. Since its introduction in the late 1960s, prenatal genetic diagnosis has evolved greatly. Serendipitious detection...
Article
Full-text available
Background: Chromosomal microarray analysis has emerged as a primary diagnostic tool for the evaluation of developmental delay and structural malformations in children. We aimed to evaluate the accuracy, efficacy, and incremental yield of chromosomal microarray analysis as compared with karyotyping for routine prenatal diagnosis. Methods: Sample...
Article
Background: Every year, 1·1 million babies die from prematurity, and many survivors are disabled. Worldwide, 15 million babies are born preterm (<37 weeks' gestation), with two decades of increasing rates in almost all countries with reliable data. The understanding of drivers and potential benefit of preventive interventions for preterm births is...
Article
This study sought to determine whether a reliable non-invasive prenatal diagnosis (NI-PND) of cystic fibrosis (CF) or spinal muscular atrophy (SMA) can be achieved through analysis of circulating fetal trophoblastic cells (CFTC). The kinetics of CFTC circulation were also studied. CFTC were isolated by isolation by size of epithelial tumour/trophob...
Article
Invasive diagnostic procedures (e.g chorionic villus sampling and amniocentesis) remain essential to the complete prenatal genetic diagnosis armamentarium. Both procedures are relatively safe in experienced hands, carrying procedure-related losses of about 1 in 400. Sensitivity of aneuploidy detection with either invasive test is near 100%, 10-15%...
Article
Pre-implantation genetic diagnosis provides prenatal genetic diagnosis before implantation, thus allowing detection of chromosomal abnormalities and their exclusion from embryo transfer in assisted reproductive technologies. Polar body, blastomere or trophectoderm can each be used to obtain requisite genetic or embryonic DNA. Pre-implantation genet...
Article
Full-text available
This retrospective cohort study was to determine the frequency and types of chromosomal abnormalities in Han Chinese women with well-documented premature ovarian failure (POF). Karyotype analysis and correlation to phenotypes were performed on 531 Chinese patients with proven POF (FSH > 40 mIU/ml) attending four reproductive centers in China. G-ban...
Article
Cytogenetic microarray analysis (CMA) in prenatal testing detects chromosome abnormalities and new genetic syndromes that would be missed by conventional cytogenetics and has the potential to significantly enhance prenatal genetic evaluation. A large Eunice Kennedy Shriver National Institute Of Child Health and Human Development (NICHD)-sponsored m...
Article
Full-text available
Premature ovarian failure (POF) is a complex heritable disorder known to be caused by chromosomal abnormalities and to date a limited number of known mutations, often autosomal. We sought to identify additional genetic loci associated with POF by performing the first large-scale genome-wide association study (GWAS). GWAS, using Affymetrix SNP 6.0 c...
Article
Full-text available
Premature ovarian failure (POF), also called primary ovarian insufficiency (POI), is defined as irregular menses in women younger than 40 years with menopausal-level serum gonadotropins [1]. Spontaneous onset POF may result from numeric and structural chromosomal abnormalities, fragile X premutations, autoimmune disorders and rare syndromes, though...
Article
Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders in which various errors in adrenal biosynthesis pathways lead to impaired cortisol secretion, possible impairment of mineralocorticoid production and androgen excess. Glucocorticoid replacement therapy is the primary treatment for CAH; however, the combination of andro...
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Full-text available
The possibility of surgical repair of fetal anomalies in utero has long tantalized obstetricians and pediatric surgeons, especially since the development of high-resolution real-time ultrasonography. The presumption has been that earlier in utero repair would provide superior outcomes for the offspring than would postnatal surgery. However, postnat...
Book
Proceedings of the 2nd World Conference – Hormonal and Genetic Basis of Sexual Differentiation Disorders and Hot Topics in Endocrinology. The meeting took place at The Eden Roc Hotel in Miami Beach, Florida, 1/15/10 – 1/17-10. Endocrinology and more specifically, the area of sexual differentiation disorders is an evolving field of medicine. The dia...
Article
Prenatal treatment of female fetuses having congenital adrenal hyperplasia (CAH) requires diagnosis of gender for genotype prior to genital differentiation. This approach currently involves chorionic villus sampling (CVS). In experienced hands CVS carries minimal risk of pregnancy loss, comparable to that associated with amniocentesis. Although off...
Article
To the Editor: We applaud the Report for its recent set of essays on sports (Mar–Apr 2010). These essays attempt to address the complex issues and challenges that competition in sports can raise to ensure that all athletes are provided an appropriate opportunity to excel in a manner understood to be “fair.” Collectively the signers of this letter h...
Article
There is controversy regarding participation in high profile competitive events by female athletes perceived as inappropriately “masculine” by competitors and others. Over 50 years, international sports bodies such as the International Olympic Committee (IOC) and the International Association of Athletics Federations (IAAF) employed - and ultimatel...
Article
Full-text available
Chromosome imbalances are the leading cause of pregnancy loss in humans and play major roles in male and female infertility. Within the past two decades, the development and application of preimplantation genetic diagnosis (PGD) has played an important role in infertility practices worldwide. The purpose of this review is to discuss, how PGD may be...
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