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*  Translocation and gross deletion breakpoints in human inherited disease and cancer I: Nucleotide composition and recombination...
Translocations and gross deletions are important causes of both cancer and inherited disease. Such gene rearrangements are nonrandomly distributed in the human genome as a consequence of selection for growth advantage and/or the inherent potential of some DNA sequences to be frequently involved in breakage and recombination. Using the Gross Rearrangement Breakpoint Database [GRaBD; www.uwcm.ac.uk/uwcm/mg/grabd/grabd.html] (containing 397 germ-line and somatic DNA breakpoint junction sequences derived from 219 different rearrangements underlying human inherited disease and cancer), we have analyzed the sequence context of translocation and deletion breakpoints in a search for general characteristics that might have rendered these sequences prone to rearrangement. The oligonucleotide composition of breakpoint junctions and a set of reference sequences, matched for length and genomic location, were compared with respect to their nucleotide composition. Deletion breakpoints were found to be AT-rich ...
http://onlinelibrary.wiley.com/doi/10.1002/humu.10254/abstract
*  Mendelian Genetics: Patterns of Inheritance and Single-Gene Disorders - Medical Genetics
By: Heidi Chial, Ph.D. (Write Science Right) © 2008 Nature Education Citation: Chial, H. (2008) Mendelian genetics: Patterns of inheritance and single-gene disorders. Nature Education 1(1) What can Gregor Mendel's pea plants tell us about human disease? Single gene disorders, like Huntington's disease and cystic fibrosis, actually follow Mendelian inheritance patterns. Mendel's studies of inheritance patterns in pea plants are a solid foundation for our current…
https://geneticamedicala.org/2013/03/30/mendelian-genetics-patterns-of-inheritance-and-single-gene-disorders/
*  Genes, mutations, and human inherited disease at the dawn of the age of personalized genomics - Cooper - 2010 - Human Mutation ...
The number of reported germline mutations in human nuclear genes, either underlying or associated with inherited disease, has now exceeded 100,000 in more than 3,700 different genes. The availability of these data has both revolutionized the study of the morbid anatomy of the human genome and facilitated "personalized genomics." With ∼300 new "inherited disease genes" (and ∼10,000 new mutations) being identified annually, it is pertinent to ask how many "inherited disease genes" there are in the human genome, how many mutations reside within them, and where such lesions are likely to be located? To address these questions, it is necessary not only to reconsider how we define human genes but also to explore notions of gene "essentiality" and "dispensability." Answers to these questions are now emerging from recent novel insights into genome structure and function and through complete genome sequence information derived from multiple individual human genomes. However, a change in focus toward ...
http://onlinelibrary.wiley.com/doi/10.1002/humu.21260/abstract
*  Preimplantation Genetic Diagnosis (PGD) | Karyomapping for single gene disorders
PGD assesses embryos to help prevent the transmission of an inherited genetic disorder. Learn about single-gene condition and translocation methods.
https://www.illumina.com/clinical/reproductive-genetic-health/preconception-fertility/pgd.html
*  Development and validation of concurrent preimplantation genetic diagnosis for single gene disorders and comprehensive...
The ADO frequency on a single cell from a fibroblast cell line was 1.64% (18/1,096). When two or more cells were tested, the ADO frequency dropped to 0.02% (1/4,426). The rate of amplification failure was 1.38% (55/4,000) overall, with 2.5% (20/800) for single cells and 1.09% (35/3,200) for samples that had two or more cells. Among 152 embryos tested in 17 cases by qPCR-based PGD and CCS, 100% were successfully given a diagnosis, with 0% ADO or amplification failure. Genotyping consistency with reference laboratory results was >99%. Another 304 embryos from 43 cases were included in the clinical application of qPCR-based PGD and CCS, for which 99.7% (303/304) of the embryos were given a definitive diagnosis, with only 0.3% (1/304) having an inconclusive result owing to recombination. In patients receiving a transfer with follow-up, the pregnancy rate was 82% (27/33).. Conclusion(s): ...
http://fertstertforum.com/zimmermanr-qpcr-based-pgd-ccs/
*  Translocation and gross deletion breakpoints in human inherited disease and cancer II: Potential involvement of repetitive...
Translocations and gross deletions are responsible for a significant proportion of both cancer and inherited disease. Although such gene rearrangements are nonuniformly distributed in the human genome, the underlying mutational mechanisms remain unclear. We have studied the potential involvement of various types of repetitive sequence elements in the formation of secondary structure intermediates between the single-stranded DNA ends that recombine during rearrangements. Complexity analysis was used to assess the potential of these ends to form secondary structures, the maximum decrease in complexity consequent to a gross rearrangement being used as an indicator of the type of repeat and the specific DNA ends involved. A total of 175 pairs of deletion/translocation breakpoint junction sequences available from the Gross Rearrangement Breakpoint Database [GRaBD; www.uwcm.ac.uk/uwcm/mg/grabd/grabd.html] were analyzed. Potential secondary structure was noted between the 5′ flanking sequence of the ...
http://onlinelibrary.wiley.com/doi/10.1002/humu.10253/abstract
*  A Potential Oligogenic Etiology of Hypertrophic Cardiomyopathy, A Classic Single Gene Disorder | Circulation Research
Rationale: Hypertrophic cardiomyopathy (HCM) is a prototypic single gene disease caused mainly by mutations in genes encoding sarcomere proteins. Despite the remarkable advances, the causal genes in about 40% of the HCM cases remain unknown, typically in small families and sporadic cases, wherein co-segregation could not be established. Objective: To test the hypothesis that the "missing causal genes" in HCM is, in part, because of an oligogenic etiology, wherein the pathogenic variants do not co-segregate with the phenotype. Methods and Results: A clinically affected trio with HCM underwent clinical evaluation, electrocardiography, echocardiography, magnetic resonance imaging, and whole exome sequencing (WES). Pathogenic variants in the WES data were identified using established algorithms. Family members were genotyped by Sanger sequencing and co-segregation was analyzed. The siblings had a severe course while the mother had a mild course. Variant analysis showed that the trio shared 145 ...
http://circres.ahajournals.org/content/early/2017/02/20/CIRCRESAHA.116.310559
*  Gene conversion causing human inherited disease: Evidence for involvement of non-B-DNA-forming sequences and recombination...
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http://onlinelibrary.wiley.com/doi/10.1002/humu.21020/pdf
*  Translocation and gross deletion breakpoints in human inherited disease and cancer II: Potential involvement of repetitive...
If you are a society or association member and require assistance with obtaining online access instructions please contact our Journal Customer Services team ...
http://onlinelibrary.wiley.com/doi/10.1002/humu.10253/pdf
*  Lirias: FINDbase: a relational database recording frequencies of genetic defects leading to inherited disorders worldwide
Frequency of INherited Disorders database (FINDbase) (http://www.findbase.org) is a relational database, derived from the ETHNOS software, recording frequencies of causative mutations leading to inherited disorders worldwide. Database records include the population and ethnic group, the disorder name and the related gene, accompanied by links to any corresponding locus-specific mutation database, to the respective Online Mendelian Inheritance in Man entries and the mutation together with its frequency in that population. The initial information is derived from the published literature, locus-specific databases and genetic disease consortia. FINDbase offers a user-friendly query interface, providing instant access to the list and frequencies of the different mutations. Query outputs can be either in a table or graphical format, accompanied by reference(s) on the data source. Registered users from three different groups, namely administrator, national coordinator and curator, are responsible ...
https://lirias.kuleuven.be/handle/123456789/159655
*  ACOG Releases First-Ever Guidance on Pregnancy in Women with Genetic Conditions - ACOG
Washington, DC - With proper management, women with certain genetic conditions are able to achieve normal pregnancy outcomes, according to a new Committee Opinion from the American College of Obstetricians and Gynecologists (ACOG). This reflects an increased understanding of these rare genetic conditions, as well as new reproductive technologies and improved medical and surgical care.. The opinion, "Identification and Referral of Maternal Genetic Conditions in Pregnancy," was released by the College's Committee on Genetics.. For women with genetic conditions, preconception evaluation by appropriate obstetrician-gynecologist specialists is recommended. This can help a woman to optimize her own health before pregnancy, review her health risks associated with pregnancy and delivery, screen the woman's partner for carrier status, counsel about potential inheritance by the offspring, and create a plan of care that encompasses the ...
https://www.acog.org/About-ACOG/News-Room/News-Releases/2015/Guidance-on-Pregnancy-in-Women-with-Genetic-Conditions
*  Evolutionary conservation and selection of human disease gene orthologs in the rat and mouse genomes | Genome Biology | Full...
Human gene mutations resulting in specific disease phenotypes were first reported in the scientific literature over 50 years ago [1, 2]. Since then, protein and nucleotide sequence changes associated with human disease have accumulated at a rapid rate. A large body of literature has appeared on human disease-associated mutations, normal sequence variation, and alterations that acquire pathological significance when combined with other deleterious alleles or second-site mutations. With this information compiled into organized databases [3, 4], it is now possible to conduct large-scale, comprehensive analyses of human disease genes. Such studies acquire additional discriminatory power with the availability of multiple genome sequences from model organisms, as comparative studies can provide novel evolutionary insights into the selective relevance of genetic changes. In the present study, we have used a collection of nearly 1,200 human disease gene sequences to perform a large-scale analysis of ...
https://genomebiology.biomedcentral.com/articles/10.1186/gb-2004-5-7-r47
*  Understanding patterns of inheritance (PowerPoint presentation)
Understanding patterns of inheritance This presentation builds on session 1 exploring patterns of inheritance Patterns of inheritance The objectives of this presentation are to: • Understand how genes are inherited • Understand the differences between the inheritance patterns associated with Autosomal dominant, Autosomal recessive, Xlinked recessive and chromosomal abnormalities • Understand that the environment can impact on some common complex conditions So how are genes passed on from parent to child? Gene • Genes in the cell nucleus are physically located on 23 pairs of chromosomes • One set of 23 chromosomes is inherited from each parent • Therefore, of each pair of genes, one is inherited from a person's mother, and one from their father Chromosome Diagram showing just one pair of the 23 pairs of chromosomes in the cell nucleus. The location of one of the genes on this chromosome is shown. Classification of genetic disorders Single Gene Disorders Alterations in single genes ...
http://slidegur.com/doc/38691/understanding-patterns-of-inheritance--powerpoint-present.
*  Thalassemias: can we reduce the national burden? | Molecular Cytogenetics | Full Text
The burden of inherited disorders of hemoglobin, the commonest group of single gene disorders in India is huge. With a population of 1.21 billion and an average prevalence of β-thalassemia carriers being around 3.5-4%, there would be 35-45 million carriers and the estimated number of births of affected babies annually would be 10,000-12,000. The carrier rates vary from 1-17% in different ethnic groups. Apart from β-thalassemia, Hb E is common in the north eastern region and in West Bengal (4 to , 50%) and Hb S is prevalent in parts of central, western and eastern India (5-40%). Thus interaction of the β-thalassemias with these Hb variants is not uncommon and can lead to a severe disorder.. One way to combat the burden is by prenatal diagnosis but the only approach to reduce the national burden is by a comprehensive community control programme. Awareness is very limited in different states (,20% among pregnant women) and the entire public health infrastructure from medical colleges to district ...
https://molecularcytogenetics.biomedcentral.com/articles/10.1186/1755-8166-7-S1-I43
*  Meta-analysis of indels causing human genetic disease: mechanisms of mutagenesis and the role of local DNA sequence complexity ...
A relatively rare type of mutation causing human genetic disease is the indel, a complex lesion that appears to represent a combination of micro-deletion and micro-insertion. In the absence of meta-analytical studies of indels, the mutational mechanisms underlying indel formation remain unclear. Data from the Human Gene Mutation Database (HGMD) were therefore used to compare and contrast 211 different indels underlying genetic disease in an attempt to deduce the processes responsible for their genesis. Each indel was treated as if it were the result of a two-step insertion/deletion process and was assessed in the context of 10 base-pairs DNA sequence flanking the lesion on either side. Several indel hotspots were noted and a GTAAGT motif was found to be significantly over-represented in the vicinity of the indels studied. Previously postulated mechanisms underlying micro-deletions and micro-insertions were initially explored in terms of local DNA sequence regularity as ...
http://onlinelibrary.wiley.com/doi/10.1002/humu.10146/abstract
*  NewYork-Presbyterian Queens - Cancer Diagnosis - Uses of Genetic Testing
Diagnostic testing. Diagnostic testing is used to identify or confirm the diagnosis of a disease or condition in a person or a family. Diagnostic testing gives a "yes" or "no" answer in most cases. It is sometimes helpful in determining the course of a disease and the choice of treatment. Examples of diagnostic testing include chromosome studies, direct DNA studies, and biochemical genetic testing.. Predictive genetic testing. Predictive genetic testing determines the chances that a healthy individual with or without a family history of a certain disease might develop that disease. There is predictive testing available for some adult-onset conditions (those diseases which manifest themselves in adulthood) such as some types of cancer, cardiovascular disease, and some single gene disorders.. Presymptomatic genetic testing. Presymptomatic genetic testing is used to determine whether persons who have a family ...
http://www.nyhq.org/diw/Content.asp?PageID=DIW007372&language=Spanish
*  PLOS ONE: Evaluation of a Novel Assay for Detection of the Fetal Marker RASSF1A: Facilitating Improved Diagnostic Reliability...
Background Analysis of cell free fetal (cff) DNA in maternal plasma is used routinely for non invasive prenatal diagnosis (NIPD) of fetal sex determination, fetal rhesus D status and some single gene disorders. True positive results rely on detection of the fetal target being analysed. No amplification of the target may be interpreted either as a true negative result or a false negative result due to the absence or very low levels of cffDNA. The hypermethylated RASSF1A promoter has been reported as a universal fetal marker to confirm the presence of cffDNA. Using methylation-sensitive restriction enzymes hypomethylated maternal sequences are digested leaving hypermethylated fetal sequences detectable. Complete digestion of maternal sequences is required to eliminate false positive results. Methods cfDNA was extracted from maternal plasma (n = 90) and digested with methylation-sensitive and insensitive restriction enzymes. Analysis of RASSF1A, SRY and DYS14 was performed by real-time PCR. Results
http://journals.plos.org/plosone/article/related?id=10.1371/journal.pone.0045073
*  Single base-pair substitutions in exon-intron junctions of human genes: nature, distribution, and consequences for mRNA...
Although single base-pair substitutions in splice junctions constitute at least 10% of all mutations causing human inherited disease, the factors that determine their phenotypic consequences at the RNA level remain to be fully elucidated. Employing a neural network for splice-site recognition, we performed a meta-analysis of 478 disease-associated splicing mutations, in 38 different genes, for which detailed laboratory-based mRNA phenotype assessment had been performed. Inspection of the ±50-bp DNA sequence context of the mutations revealed that exon skipping was the preferred phenotype when the immediate vicinity of the affected exon-intron junctions was devoid of alternative splice-sites. By contrast, in the presence of at least one such motif, cryptic splice-site utilization, became more prevalent. This association was, however, confined to donor splice-sites. Outside the obligate dinucleotide, the spatial distribution of pathological mutations was found to differ significantly from that of ...
http://onlinelibrary.wiley.com/doi/10.1002/humu.20400/abstract
*  Technical Information
Ravgen's focus is testing for single gene disorders, cystic fibrosis, sickle cell anemia, and prenatal paternity testing. Contact us at (410) 715-2111.
http://www.ravgen.com/technical-information/
*  4dx2 - Proteopedia, life in 3D
The TRPV4 calcium-permeable cation channel plays important physiological roles in osmosensation, mechanosensation, cell barrier formation, and bone homeostasis. Recent studies reported that mutations in TRPV4, including some in its ankyrin repeat domain (ARD), are associated with human inherited diseases including neuropathies and skeletal dysplasias, probably due to increased constitutive activity of the channel. TRPV4 activity is regulated by the binding of calmodulin and small molecules such as ATP to the ARD in its cytoplasmic N-terminus. We determined structures of ATP-free and -bound forms of human TRPV4-ARD and compared them with available TRPV-ARD structures. The third inter-repeat loop region (Finger 3 loop) is flexible and may act as a switch to regulate the channel activity. Comparisons of TRPV-ARD structures also suggest an evolutionary link between ARD structure and ATP binding ability. Thermal stability analyses and molecular dynamics (MD) simulations suggest that ATP increases ...
http://proteopedia.org/wiki/index.php/4dx2
*  human genetic disease - Genetics of cancer | Britannica.com
human genetic disease - Genetics of cancer: Although at least 90 percent of all cancers are sporadic, meaning that they do not seem to run in families, nearly 10 percent of cancers are now recognized as familial, and some are actually inherited in an apparently autosomal dominant manner. Cancer may therefore be considered a multifactorial...
https://www.britannica.com/science/human-genetic-disease/Genetics-of-cancer
*  STR content in the exons of human disease genes. Absolu | Open-i
STR content in the exons of human disease genes. Absolute STR amount for human reference genes and the four sets of disease genes with number of genes shown in
https://openi.nlm.nih.gov/detailedresult.php?img=PMC2543027_1471-2164-9-410-5&req=4
*  Genetic conditions and inherited cancers - Causes and risk factors - Macmillan Cancer Support
You might be offered the chance to test for some genetic conditions. It's important to understand what might happen and the effect any possible results might have.
https://www.macmillan.org.uk/information-and-support/diagnosing/causes-and-risk-factors/genetic-testing-and-counselling
*  Model Discusses Rare Genetic Condition Affecting Her Appearance
Meet a young woman with a rare genetic condition that dramatically affects her appearance. Plus, see the incredible surprises The Doctors have in store...
http://www.thedoctorstv.com/articles/2871-model-discusses-rare-genetic-condition-affecting-her-appearance
*  RFA-DK-03-008: GENETIC MODIFIERS OF MENDELIAN DISEASES OF INTEREST TO NIDDK
NIH Funding Opportunities and Notices in the NIH Guide for Grants and Contracts: GENETIC MODIFIERS OF MENDELIAN DISEASES OF INTEREST TO NIDDK RFA-DK-03-008. NIDDK
https://grants.nih.gov/grants/guide/rfa-files/RFA-DK-03-008.html