Editorial Reviews. From the Back Cover. This fourth edition of the best-selling textbook, Human Genetics and Genomics, clearly explains the key principles. Now featuring full-color diagrams, Human Genetics and Genomics has been fully supported by a suite of online resources at wfhm.info, including: . This fourth edition of the best-selling textbook, HumanGenetics and Genomics, clearly explains the key principlesneeded by medical and health sciences.
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Human Genetics and Genomics - RESOURCES. Welcome to the companion resources site for the Fourth Edition of Human Genetics and Genomics. On this site. GENETIC CONDITIONS. Select a topic from the list below to view or download the relevant information (PDF format). You are free to download the material on. immunogenetics, human genomics, genomics of complex diseases, genomic methods of 'Genetics and Genomics' held in Semmelweis University for medical.
A newly expanded Part 1, Basic Principles of Human Genetics, focuses on introducing the reader to key concepts such as Mendelian principles, DNA replication and gene expression.
Part 2, Genetics and Genomics in Medical Practice, uses case scenarios to help you engage with current genetic practice. The perfect companion to the genetics component of both problem-based learning and integrated medical courses, Human Genetics and Genomics presents the ideal balance between the bio-molecular basis of genetics and clinical cases, and provides an invaluable overview for anyone wishing to engage with this fast-moving discipline.
Korf is Wayne H. Mira B. Permissions Request permission to reuse content from this site. The perfect companion to the genetics component of both PBL and Integrated medical courses, Human Genetics and Genomics 4e, presents the perfect balance between the bio molecular basics of genetics and clinical cases and snapshots, and is fully supported with online supplements.
NO YES. Selected type: Added to Your Shopping Cart. Genome-Scale Sequencing in Children The technology to enable whole-exome sequencing and whole-genome sequencing has become more accurate, more efficient, and less expensive. These cost estimates are for the generation of sequence data and do not include the clinical interpretation of the information. Given these technical improvements, genome-scale sequencing can be considered in a variety of clinical and research contexts.
These include diagnostic testing, predictive testing for childhood-onset conditions, pharmacogenetic testing, and testing in children with cancer to inform diagnosis or therapy. Yet, the improving coverage, accuracy, sensitivity, and cost effectiveness of genome-scale sequencing will eventually equal that of testing a single gene or performing targeted gene panels, meaning that genome-scale sequencing might become an attractive choice for interrogating a single gene or targeted set of genes.
The ASHG recognizes the current debate regarding the obligation, if any, to search for selected variants with high clinical validity and clinical utility when conducting genome-scale sequencing.
When genome-scale sequencing is performed but the analysis is restricted to a limited set of targeted genes, ASHG finds it ethically acceptable for the laboratory to limit the analysis to the genes of clinical interest. Depending on the clinical presentation and on the quality and availability of appropriate targeted testing, comprehensive testing such as genome-scale sequencing might also be indicated in certain circumstances, even in the absence of prior, more limited genetic testing.
Accordingly, genome-scale sequencing is not indicated for the purposes of clinical newborn screening at this time.
In the research setting, genome-scale sequencing in newborns for screening purposes can be justified as part of carefully developed protocols for better understanding the potential benefits and risks of this technology in this context.
Secondary Findings The move from targeted genetic testing to genome-scale sequencing has led to a vigorous debate about the ethics of managing massive amounts of individual-level genetic data. See, e. Secondary findings might have a clinical utility for a child or his or her family members. Parents or guardians should have a clear understanding of when secondary findings might be generated and of the circumstances, if any, under which they can expect to be offered results.
Children should be included in the informed-assent or -consent process to the extent that they are capable. Parents have wide decision-making authority, but in cases where the clinical response to a secondary finding will most likely prevent serious morbidity or mortality for the child, it can be appropriate to override a parental decision not to receive this information.
There is an ongoing debate about the extent to which researchers are obligated to disclose secondary findings to research participants. Research and clinical care have distinct characteristics, and the responsibility of a clinician necessarily differs from that of a researcher.
Although they are generally distinct, the line between research and clinical care is often blurry, particularly in the context of genomics.
Questions about whether there is a duty to look for secondary findings have been actively debated. However, more data, experience, and debate are necessary for defining the most ethically appropriate approach in the clinical pediatric context regarding an obligation to look for secondary findings.
In the research context, the ethical responsibilities and risk-benefit considerations differ from the clinical context. Therefore, actively searching for secondary findings in research involving genome-scale sequencing might be ethically acceptable in certain circumstances with the informed consent of parents but should not be considered ethically required at the present time.
CMA The transition from chromosome analysis by karyotype to the utilization of CMA has transformed genetic diagnostics. CMA also has the potential to identify secondary findings. This list could function as a secondary-findings list with implications for what should and should not be reported back to families.
Clinicians should understand the concepts of variants of uncertain significance, variable expressivity, and reduced penetrance and the potential need to consider testing of other family members. Carrier Testing of Adolescents Carrier testing of adolescents has historically been controversial, and professional statements generally do not support routine carrier testing of adolescents outside of pregnancy or reproductive planning. Outside of some specific populations e.
In contrast, adult siblings of individuals affected by recessive or X-linked conditions often have strong views on whether or not they wish to know their carrier status and how it might affect their reproductive decision making.
Some studies have reported that siblings show transient anxiety and depression after carrier testing. Additionally, these studies also suggested that adolescents found to be carriers felt able to plan for future parenthood and that most were open about the condition and their carrier status, sharing with family, and planning to tell partners.
Adolescent assent and parental consent should be obtained for carrier testing, and genetic counseling might be appropriate in some circumstances.
Carrier testing could be performed on children in other less well-studied settings, including institutional settings such as high school, college, or athletic programs. Outcome studies in this area are somewhat limited and generally describe carrier testing offered in high schools in Canada, Australia, and the Netherlands.
These studies, performed over 20 years, have shown high uptake rates and have not demonstrated adverse psychological consequences. Research projects to further evaluate adolescent carrier testing in institutional contexts is appropriate with carefully drafted protocols. Direct-to-Consumer Testing Direct-to-consumer genetic testing DTC GT refers to genetic testing that bypasses the involvement of health-care providers and is sold directly to consumers.
DTC GT is marketed to consumers primarily via the internet and was initially limited to paternity and ancestry testing. However, DTC GT has in recent years been expanded to offer testing for potential health-related claims. DTC GT offers individuals the opportunity to have access to personal genetic information.
In one study of interviews conducted with clinicians who offered genomic-risk assessment to patients, the clinicians appeared to have learned most of what they know about genomics directly from the commercial laboratories. In response to such marketing claims, the FDA prohibited 23andMe from selling its personal-genome service in November Ten of those 13 companies performed testing of minors in response to requests from parents or legal guardians.
Three companies would consider testing if it was requested by a minor. Information on DTC GT websites might not be balanced with regard to how they present risks and benefits. Users of the test might consent to testing without understanding the full consequences of the results.
Pharmacogenomic Testing Pharmacogenetic testing in adults and in children has the potential to improve drug efficacy and reduce adverse events. However, research on pharmacogenetic testing in children has been limited, so there is little current evidence on the potential benefits and harms associated with this type of genetic testing.
Further, pharmacogenetic data can account for some, but not all, variability in drug response and therefore should be considered in conjunction with other factors in clinical pharmacologic decision making. CYP2C19, an enzyme that is involved in a number of commonly prescribed drugs, is one example in which genotypically predicted extensive normal metabolizers can have a poor metabolizer phenotype in the first few months of life.
Pharmacogenetic testing has been proposed for clinical use and is supported by varying levels of evidence in many medical specialties, including but not limited to oncology, rheumatology, psychiatry, HIV treatment, immunosuppression, and anticoagulation. Newborn Screening Newborn screening NBS is one of the most effective public-health programs of the last century. NBS is conducted by state-based public-health programs in the US.
For the first four decades of the programs, there was substantial variability between states on the conditions targeted. The SACHDNC was established in through federal legislation with the primary goal of establishing an evidence-review process to make recommendations for conditions on a uniform screening panel.
Given the low prevalence of most conditions targeted by NBS, making informed policy decisions regarding the introduction of new tests is challenging. State NBS programs are designed to both enable affected children to receive a prompt, accurate diagnosis and coordinate short-term clinical care for the condition. However, health departments do not typically collect data on the longer-term outcomes for children or their families.
Further, the low prevalence of many conditions targeted through NBS makes it difficult to conduct outcomes research without large, multicenter projects.
Therefore, data on the clinical outcomes of affected children, with or without NBS, is often limited. Such infrastructures would support the ability to assess outcomes and to conduct controlled trials of therapeutic options and evaluate support systems required for affected children and their families. NBS is conducted on dried bloodspots collected from the infant within the first few days of life.
Although all state programs provide information to parents about NBS, usually in the form of a brochure, the literature shows that most parents do not read this information.
Accordingly, most parents have little awareness and understanding of NBS. The literature demonstrates that parents want to be informed, but most only want basic facts about NBS programs.
However, 43 states permit parents to refuse NBS for either religious or philosophical reasons. The number of parents who opt out of NBS is exceedingly small. State programs typically are strongly supportive of the current opt-out approach because a formal permission process is cumbersome, particularly if signed consent forms are required, and could increase the risk that newborns will not be screened. Obtaining truly informed permission for NBS during the postnatal period is challenging because of the hectic environment, the short hospitalization for many newborns, and the many competing priorities for parents and newborn-care providers.
Further, signatures to document permission can be obtained in a perfunctory fashion, so requiring signatures per se does not assure a meaningful informed-permission process.
Under the assumption that parents are reasonably informed about the program and their rights under state law, both opt-in and opt-out approaches to NBS are ethically acceptable. When screening is conducted, programs obtain sufficient blood from infants to perform all testing and to conduct repeat testing when warranted. This means that most infants will have extra blood on the filter cards after screening.
Traditionally, many states have saved these residual dried bloodspots DBSs for several purposes, including quality assurance QA for NBS laboratory services, forensic uses, and biomedical research.
Genetics, Genomics and Informatics
Although many states discard the DBSs after screening is complete, many states retain these DBSs for various lengths of time. The retention of DBSs became controversial in recent years when two state programs, those of Minnesota and Texas, were sued by parent groups for the lack of parental permission for this practice.
In the US and Canada, research on public attitudes regarding the management of DBSs demonstrates broad public support for the retention of DBSs for QA and biomedical research, contingent on parental education and choice. Prior to , when used for biomedical research, residual DBSs were typically de-identified, or research was conducted under a waiver of parental permission. The impact of this law on NBS-related research remains to be determined.
Retention for QA purposes should be considered integral to the NBS program and should not require specific permission from parents. This choice ought to be clearly separated from the decision to participate in NBS. Information relevant to reproductive risk is also provided by the generation of results related to carrier status.
Disclosure of carrier status through NBS raises challenges because this information is not typically available without informed consent and is not usually provided to minors. However, there is limited evidence to support the utility and impact of disclosing carrier results to families.
A stronger evidentiary base is required to inform evidence-based decision making and recommendations. Prospective adoptive parents might want genetic information about a child to inform their decision on whether or not to adopt.
But previous consensus statements of the ASHG and ACMG have advocated that indications for pre-adoption testing closely parallel the indications applied to children living with their biological parents. If such concerns are valid for children living with their biological parents, then the standards for genetic testing should be the same for all children.
It has been suggested that it is in the interest of the child to be placed with families who are optimally capable of taking care of their medical needs.
A commonly held view is that it would disadvantage the child to be placed with some adoptive parents and that even factors such as cultural and ancestral education should be considered. It is possible that a child with an untreatable genetic disorder would be better off with parents specifically chosen because of their ability to deal with this difficult circumstance.
However, there is no assertion of a parallel responsibility of the prospective parents to undergo genetic testing themselves. The argument of matching creates the possibility that some parents might find themselves to be genetically unsuitable to adopt.
We endorse and affirm the previous recommendations of the ASHG. Consanguinity Inbreeding, including first-degree relative relationships, could be detected in genome-wide assays including but not restricted to SNP genotyping, whole-exome sequencing, and whole-genome sequencing. If AOH is confined to a single chromosome, the cause could be a chromosome replication or segregation abnormality uniparental isodisomy [UPD].
In UPD, the person undergoing testing has received identical copies of one parental homolog for part or all of a chromosome. The length of the homozygous segment will usually distinguish UPD from autozygosity—identical chromosome segments inherited from the mother and father as a result of a recent shared ancestor.
In contrast, if there are multiple long AOH segments with AOH involving many or all of the chromosomes, the most likely explanation is that the parents are close biological relatives. The motivation for genetic testing might be to detect a diagnostically important DNA copy-number abnormality or single-gene disorder. But the finding of AOH cannot be considered purely incidental because UPD detection is a formal reason for diagnostic testing.
UPD or autozygosity can be a necessary condition for imprinting defects or homozygous recessive disorders.
Disclosure of the results should, therefore, be guided by the same principles as those for other diagnostic testing. The detection of extensive long segments of AOH is most consistent with reproduction between close relatives. In the absence of a history of assisted reproduction, this implies incest.
The central concern for practitioners is the possibility of sexual abuse of a minor. Sexual relations between close relatives are illegal in most jurisdictions, but the specifics of the laws vary in how relatedness is specified. Physician-patient confidentiality must be respected in most circumstances. An important exception is the circumstance in which the health-care provider suspects that a child is being abused.
Physicians are obligated to report suspected child abuse without exception. It does not necessarily follow that the possibility of discovering information that could lead to a suspicion of child abuse should be presented in pre-test counseling. For most patients, this information will be irrelevant but could cause unnecessary anxiety and could even lead to the refusal to allow a diagnostic test. Practitioners should develop procedures for case management when genetic laboratory results are consistent with incest involving a minor.When genome-scale sequencing is performed but the analysis is restricted to a limited set of targeted genes, ASHG finds it ethically acceptable for the laboratory to limit the analysis to the genes of clinical interest.
The motivation for genetic testing might be to detect a diagnostically important DNA copy-number abnormality or single-gene disorder.
Genomic Medicine XI: Research Directions in Genomic Medicine Implementation
Published by Elsevier Ltd. Research and clinical care have distinct characteristics, and the responsibility of a clinician necessarily differs from that of a researcher. Carrier Testing of Adolescents Carrier testing of adolescents has historically been controversial, and professional statements generally do not support routine carrier testing of adolescents outside of pregnancy or reproductive planning.
The ethical, legal, and social issues in genetic and genomic testing have been subject to special scrutiny for several reasons. Users of the test might consent to testing without understanding the full consequences of the results. If such concerns are valid for children living with their biological parents, then the standards for genetic testing should be the same for all children.
Some studies have reported that siblings show transient anxiety and depression after carrier testing. The argument of matching creates the possibility that some parents might find themselves to be genetically unsuitable to adopt.
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