scholarly journals The genetic basis of infertility

Reproduction ◽  
2003 ◽  
pp. 13-25 ◽  
Author(s):  
K Shah ◽  
G Sivapalan ◽  
N Gibbons ◽  
H Tempest ◽  
DK Griffin
Keyword(s):  
Genetic Basis ◽  
Chromosomal Abnormalities ◽  
Klinefelter Syndrome ◽  
Single Gene ◽  
Chromosome Translocations ◽  
Susceptibility To Infection ◽  
Single Gene Disorders ◽  
Males And Females ◽  
One Year ◽  
Specific Disorders

Infertility is defined as the inability to conceive after one year of regular unprotected intercourse; approximately one in six couples wishing to start a family fall into this category. Although, in many cases, the diagnosis is simply 'unexplained', a variety of reasons including lack of ovulation, mechanical stoppage, sperm deficiencies and parental age have been implicated. It is difficult to assess accurately the overall magnitude of the contribution of genetics to infertility as most, if not all, conditions are likely to have a genetic component, for example susceptibility to infection. Nevertheless, a significant number of infertility phenotypes have been associated with specific genetic anomalies. The genetic causes of infertility are varied and include chromosomal abnormalities, single gene disorders and phenotypes with multifactorial inheritance. Some genetic factors influence males specifically, whereas others affect both males and females. For example, chromosome translocations affect both males and females, whereas Klinefelter syndrome and the subsequent infertility phenotype caused by it are specific to males. This article reviews current research in the genetic basis of infertility; gender-specific disorders and those affecting both sexes are considered.

Reaching Future Scientists, Consumers, & Citizens

2014 ◽  
Vol 76 (6) ◽  
pp. 379-383 ◽  
Author(s):  
Melissa A. Hicks ◽  
Rebecca J. Cline ◽  
Angela M. Trepanier
Keyword(s):  
Personalized Medicine ◽  
Genetic Basis ◽  
Genetic Disorders ◽  
Single Gene ◽  
Personal Health ◽  
Adult Onset ◽  
Biology Textbooks ◽  
Multifactorial Diseases ◽  
Single Gene Disorders

An understanding of how genomics information, including information about risk for common, multifactorial disease, can be used to promote personal health (personalized medicine) is becoming increasingly important for the American public. We undertook a quantitative content analysis of commonly used high school textbooks to assess how frequently the genetic basis of common multifactorial diseases was discussed compared with the “classic” chromosomal–single gene disorders historically used to teach the concepts of genetics and heredity. We also analyzed the types of conditions or traits that were discussed. We identified 3957 sentences across 11 textbooks that addressed multifactorial and “classic” genetic disorders. “Classic” gene disorders were discussed relatively more frequently than multifactorial diseases, as was their genetic basis, even after we enriched the sample to include five adult-onset conditions common in the general population. Discussions of the genetic or hereditary components of multifactorial diseases were limited, as were discussions of the environmental components of these conditions. Adult-onset multifactorial diseases are far more common in the population than chromosomal or single-gene disorders; many are potentially preventable or modifiable. As such, they are targets for personalized medical approaches. The limited discussion in biology textbooks of the genetic basis of multifactorial conditions and the role of environment in modifying genetic risk may limit the public’s understanding and use of personalized medicine.

Genetics

2019 ◽  
pp. 341-348
Keyword(s):  
Birth Defects ◽  
Trisomy 21 ◽  
Chromosomal Abnormalities ◽  
Familial Cancer ◽  
Single Gene ◽  
Medical Specialty ◽  
Clinical Genetics ◽  
Single Gene Disorders ◽  
Familial Cancer Syndromes ◽  
Cancer Syndromes

Clinical genetics is the medical specialty that deals with diagnosis and counselling of patients affected (or potentially affected) with disease that may have a genetic basis. These conditions include chromosomal abnormalities (e.g. Down’s syndrome/trisomy 21), single gene disorders (e.g. cystic fibrosis), familial cancer syndromes (e.g. hereditary non-polyposis colorectal cancer), and birth defects with a genetic component (e.g. cleft palate). The service is largely consultant led, supported by genetic counsellors in tertiary referral centres. Different inheritance patterns are described, autosomal dominant, autosomal recessive, X-linked, and mitochondrial, as well as the range of different genetic tests currently in clinical use (karyotype, microarray, gene panel, exome sequencing, and genome studies). The importance of empathetic communication, a detailed family history, and a multidisciplinary approach are emphasized.

scholarly journals The genetic basis of disease

2018 ◽  
Vol 62 (5) ◽  
pp. 643-723 ◽  
Author(s):  
Maria Jackson ◽  
Leah Marks ◽  
Gerhard H.W. May ◽  
Joanna B. Wilson
Keyword(s):  
Human Disease ◽  
Genetic Basis ◽  
Single Gene ◽  
Complex Disorders ◽  
Chromosomal Imbalances ◽  
Technological Advances ◽  
Single Gene Disorders ◽  
All Diseases

Genetics plays a role, to a greater or lesser extent, in all diseases. Variations in our DNA and differences in how that DNA functions (alone or in combinations), alongside the environment (which encompasses lifestyle), contribute to disease processes. This review explores the genetic basis of human disease, including single gene disorders, chromosomal imbalances, epigenetics, cancer and complex disorders, and considers how our understanding and technological advances can be applied to provision of appropriate diagnosis, management and therapy for patients.

scholarly journals Prevalence of Abnormal Karyotypes among Males with Non-obstructive Azoospermia and Severe Oligozoospermia: A Retrospective Study

2021 ◽  
Author(s):  
Priya Narayanan ◽  
PR Ashalatha
Keyword(s):  
Chromosomal Abnormalities ◽  
Klinefelter Syndrome ◽  
Semen Analysis ◽  
Marker Chromosome ◽  
Gene Mutations ◽  
Obstructive Azoospermia ◽  
Transmembrane Conductance Regulator ◽  
Severe Oligozoospermia ◽  
Polymorphic Variants ◽  
Specific Disorders

Introduction: Chromosomal abnormalities are one of the important causes of male infertility. Numerical and structural chromosomal abnormalities are seen frequently in men with azoospermia and severe oligospermia. Other abnormalities include Y Chromosome Microdeletions (YCMD), Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene mutations affecting the internal ductal system, genes affecting sperm function and other non-specific disorders. Upto 14% of the men with azoospermia and severe oligospermia have karyotypic abnormalities. Aim: To determine the prevalence of abnormal karyotypes among men with azoospermia and severe oligozoospermia (<5 million/mL). Materials and Methods: The present study was a retrospective observational study carried out at the Fertility Clinic, Institute of Maternal and Child Health, Calicut, Kerala, India, on patients who attended the Infertility Department between January 2016 to December 2019. Semen analysis was done on 232 patients with 100 patients of azoospermia and 132 patients of oligozoospermia. Karyotyping was done from the Cytogenetics Unit, Department of Anatomy. The data was entered in MS excel sheet and analysed and results were expressed in percentage. Results: Chromosomal abnormalities were detected in 35 (35%) of 100 azoospermia and 15 (11.3%) of 132 severe oligospermia cases analysed. Klinefelter syndrome was the most common abnormality detected in azoospermia (22/35). A 46XX was found in two cases. Structural abnormalities were detected in three case (46 X, der X, 46XY der Chr 1 and Chr 9 inversion). Small Y was found in three cases. Polymorphic variants were found in five patients (46XY 15pstk+, 46XY 15ps+, 46XY 1qh+, 46XY 9qh+). Small Y was found in one case. In oligozoospermia, autosomal translocations were found in four cases {46XY, t(11;13)(q21;q21.2), 46XY, t(1;9) (p13;p21), 46XY, t(13;15)(q34;q21), 46XY, t(7,14) (q34:q11)}, Derivative (46XY der 15) and Marker chromosome (47XY+mar) in one case each. Klinefelter syndrome was found in two cases and 48XXYY was found in one patient. Polymorphic variants were found in five cases (46XY 21pstk,46XY 15ps+, 46XY 1qh-, 48XY 9qh+). Small Y was found in one case. Conclusion: Sex chromosomal and autosomal abnormalities are found frequently in azoospermia and severe oligospermia and hence, genetic screening and counseling before Intracytoplasmic Sperm Injection (ICSI) is warranted.

P4647Next generation sequencing in 83 fetal left-sided CHDs reveals the entire genetic architecture of left-sided CHDs in fetal population

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
H R Sun ◽  
X Y Hao ◽  
T Yi ◽  
X Y Gu ◽  
Y H He
Keyword(s):  
Genetic Architecture ◽  
Chromosomal Abnormalities ◽  
Heart Defects ◽  
Large Fraction ◽  
Single Gene ◽  
Copy Number Variants ◽  
Terminal Deletion ◽  
Pathogenic Variants ◽  
Single Gene Disorders ◽  
Low Pass

Abstract Background No data is available for the contribution of single gene disorders (SGDs) to left-sided congenital heart defects (LSCHDs) in the fetal population. Purpose The aim of this study was to explore the entire genetic architecture of LSCHDs, especially the contribution of SGDs in a cohort of fetal LSCHDs. Methods Low-pass whole genome sequencing (WGS) and whole exome sequencing (WES) were performed on specimens from 83 deceased fetuses with lSCHDs, including 48 HLHS, 22 CoA, 5 AS, 3 AAH, 2 AS+CoA and 1 case of AA, AS+MS, MA. Sequencing was predominantly performed in fetus-parent trios (n=63, 75.9%), or in fetus only (n=20, 24.1%). Results 34.9% (n=29) of the 83 fetal left-sided CHDs were identified with related genetic abnormalities. WGS analysis identified 14 (16.9%) with chromosomal abnormalities, including 6 (7.2%) aneuploidies and 8 (9.6%) pathogenic copy number variants (CNVs). WES analysis of the remaining 69 cases without chromosomal abnormalities identified 15 (15/69, 21.7%) with pathogenic/likely pathogenic variants. Of these 15 cases, KMT2D was the most frequently mutated gene (7/69, 10.1%), followed by NOTCH1 (4/69, 2.5%). Compound heterozygosity was identified in 3 genes (DNAH11, POFUT1, CRB2) that are not yet well established as CHD genes. Finally, we also observed a LOF variant in NONO (X-linked) that was maternally transmitted to an affected male case. The genetic results of this cohort Aneuploidies Trisomy 18 4 Turner syndrome 2 CNVs 11q terminal deletion 3 1p36 deletion 1 15q terminal deletion 1 7q11.23 deletion 1 4p terminal deletion 1 12q complex internal duplication 1 SGDs AD (KMT2D = 7; NOTCH1 = 4) 11 AR (DNAH11, POFUT1, CRB2) 3 X-recessive (NONO) 1 AD: autosomal dominant; AR: autosomal recessive. Conclusions Our experience supports that SGDs contribute a significant part to the pathogenesis of fetal CHDs, WES has the potential to provide molecular diagnoses in fetal left-sided CHDs without chromosomal abnormalities. KMT2D mutations accounted for a large fraction of left-sided CHDs in fetal population. If the KMT2D mutation is detected, further diagnosis of Kabuki syndrome should be considered.

Further Clinical Delineation of Chromosome 1q21Microduplication Syndrome: Robin Sequence as an Under-Recognized Association in Chromosomal Microdeletions and Duplications

2020 ◽  
pp. 105566562095475
Author(s):  
Lauren K. Salinero ◽  
Natasha Shur ◽  
Albert K. Oh
Keyword(s):  
Genetic Testing ◽  
Congenital Anomalies ◽  
Chromosomal Abnormalities ◽  
Single Gene ◽  
Airway Intervention ◽  
Robin Sequence ◽  
Single Gene Disorders ◽  
Surgical Airway ◽  
Chromosome 1Q21

Robin sequence (RS) has been reported in association with single gene disorders and chromosomal abnormalities; however, it has not previously been described in connection with chromosome 1q21 microduplication. We present the first known case of a neonate diagnosed with chromosome 1q21.1 microduplication syndrome and RS requiring surgical airway intervention. This case demonstrates the value of genetic testing in cases of RS presenting with other congenital anomalies.

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