Clinical Genomics

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Questions and Answers

What was the observed range of postzygotic de-novo mutations in the monozygotic twin GWAS studies?

5 – 20

10 – 30

15 – 48 (correct)

50 – 70

Where were more post-zygotic mutations observed according to the text?

DNA from blood than oral mucosa (correct)

DNA from oral mucosa than blood

Equal in DNA from blood and oral mucosa

Not mentioned in the text

What did deCODE observe in one twin pair in terms of discordant de novo mutations?

25,653 discordant de novo mutations (correct)

10,000 discordant de novo mutations

5,000 discordant de novo mutations

50,000 discordant de novo mutations

What is the main focus of Geisinger's MyCode goals and focus areas?

Linking genomes to phenomes Signup and view all the answers

Why does comparing a patient’s genome to a reference genome not readily inform about the potential causative gene?

Variation in individual genomes and complex genetic interactions Signup and view all the answers

What does trio whole genome sequencing more readily allow for, compared to comparison of a proband’s genome to a reference genome?

Variant calling Signup and view all the answers

How can nationalized medicine and genomics result in personalized medicine from cradle to grave?

By tailoring medical interventions based on individual genetic information Signup and view all the answers

What is the main focus of Geisinger’s MyCode initiative?

Screening for disease risk alleles Signup and view all the answers

Which organization has funded a $50M project to sequence UK Biobank samples?

A consortium with Regeneron and others in Big Pharma Signup and view all the answers

What is the main purpose of ClinGen's tools?

Defining the clinical relevance of genes and variants Signup and view all the answers

What does the Medical Genome Reference Bank aim to understand?

The genome as people age Signup and view all the answers

What is the key focus of Geisinger’s Genomic Medicine Institute?

Development of precision medicine Signup and view all the answers

What is the main risk conditions studied in Geisinger’s MyCode initiative?

CDC tier 1 conditions, cardiovascular risks, cancer, and other conditions Signup and view all the answers

What is the goal of Geisinger’s MyCode initiative in terms of participant data sets?

Reaching 2 million patient data sets for analysis Signup and view all the answers

What does the American College of Medical Genetics and Genomics note as current challenges?

Incorporation into electronic health records, patient accessibility, and linking genomic data to clinical decision support tools Signup and view all the answers

What is the collaboration between Geisinger and Regeneron focused on?

Analyzing samples and accessing de-identified genomic and phenomic data for drug development and variant discovery Signup and view all the answers

What is the focus of the UK and several Nordic countries in terms of data collection?

Collecting phenomic-genomic data for disease diagnosis and research Signup and view all the answers

What is the main focus of the eMERGE project led by Geisinger’s Genomic Medicine Institute?

Development of precision medicine Signup and view all the answers

What is the average time for diagnosis of undiagnosed diseases in the US?

7.6 years Signup and view all the answers

What is the main source of DNA used for the analysis of genomic and physiological features in individuals over 70?

Blood Signup and view all the answers

What has been observed in males over 70 in terms of genomic changes?

Decline in Y-copy number Signup and view all the answers

What is clonal hematopoiesis?

Abnormal growth of blood cells Signup and view all the answers

What is the main challenge in genetic diagnosis of diseases?

Low frequency of mono-genetic diseases Signup and view all the answers

What has improved diagnosis rates by about 10%?

Sharing phenomic and genomic data Signup and view all the answers

What method is NOT mentioned as a diagnostic method for undiagnosed diseases?

Genetic engineering Signup and view all the answers

What has been leveraged for diagnosis through data synthesis and the development of Face2Gene?

Artificial intelligence Signup and view all the answers

Which company conducts several GWAS and trio/twin studies leveraging unique population genetics and social features?

deCODE Signup and view all the answers

What does a trio study on recombination frequency show?

Maternal age effects on crossover number Signup and view all the answers

What is the cost of targeted sequencing using phenomic linking per person?

$1,000 Signup and view all the answers

What is a current challenge related to insurance coverage for genomic sequencing in children and adults?

Lack of insurance coverage Signup and view all the answers

What are the clinical utility considerations of genomic sequencing?

Technical efficacy, diagnostic accuracy efficacy, and therapeutic efficacy Signup and view all the answers

What is a current challenge in the use of EHR for genomic medicine?

Lack of standards to represent and communicate genomic information Signup and view all the answers

What is the role of family physicians in Canada in integrating genomic medicine into primary care?

Developing family history/pedigrees, making referrals, and supporting patients with genetic diseases Signup and view all the answers

What should educational resources for primary care practice in genomic medicine include?

Case studies starting with the first presentation of the patient in the primary care setting Signup and view all the answers

What methods are involved in phenomic methods?

Digitized patient data, patient interview/history, and data consolidation in digital format Signup and view all the answers

What is the focus of integrating genomic medicine into primary care in Canada?

Developing family physician questionnaires Signup and view all the answers

What is the main focus of the study authored by Dr. Darl Ray Swartz?

Integrating genomic medicine into healthcare Signup and view all the answers

What is the role of most hospitals' EHR in relation to genomic data?

Data entry, analysis for treatment, and rapid communication Signup and view all the answers

What is the focus of cascade (family) whole genome or exome sequencing?

Identification of inheritance and recombination sites Signup and view all the answers

What is the main method mentioned for Genome Analytical/Diagnostic Methods?

Multiplex PCR panels and custom microarrays Signup and view all the answers

Study Notes

Genomic Changes with Aging and Undiagnosed Diseases

Analysis of genomic and physiological features in individuals over 70 using blood as a DNA source
Findings include decline in mitochondrial number and Y-copy number in males, increase in somatic variant burden and clonal hematopoiesis
Medical Genome Reference Bank contains whole genome and phenome data for 2,570 healthy elderly
Undiagnosed diseases refer to conditions with no documented diagnosis, estimated at 7,000 diseases with an average 7.6 years for diagnosis in the US
Genetic difficulty in determining diseases due to low frequency of mono-genetic diseases and complex heterozygote conditions
Efforts to share phenomic and genomic data through consortia for better diagnosis using human phenotype ontology
Diagnostic methods for undiagnosed diseases include karyotyping, chromosomal microarray, exome sequencing, and proteomics
Combining biological knowledge from cell and animal models has improved diagnosis rates by about 10%
Leveraging artificial intelligence and deep-learning for diagnosis through data synthesis and the development of Face2Gene
DeCODE, an Iceland company, conducts several GWAS and trio/twin studies leveraging unique population genetics and social features
Trio study on recombination frequency shows crossover hotspots, complex crossovers, and maternal age effects on crossover number
Crossover results in de novo mutations, mostly in non-coding regions potentially modifying transcription of nearby coding genes

Integrating Genomic Medicine into Healthcare

Genome Analytical/Diagnostic Methods include multiplex PCR panels for specific diseases and custom microarrays for genetic counseling or treatment.
Targeted sequencing using phenomic linking is available at a cost of around $1,000 per person.
Cascade (family) whole genome or exome sequencing allows for the identification of inheritance and recombination sites and can help in identifying candidate genes based on potential mode of transmittance.
Insurance coverage for genomic sequencing in children and adults is a current challenge.
Phenomic methods involve digitized patient data, patient interview/history, and the consolidation of data in digital format initiated by the Dept. of Health and Human Services.
Most hospitals now use EHR for data entry and analysis for treatment, which allows for rapid communication and data mining when linked with genomic data.
Clinical utility of genomic sequencing considerations include technical efficacy, diagnostic accuracy efficacy, and therapeutic efficacy.
Current challenges in the use of EHR for genomic medicine involve a lack of standards to represent and communicate genomic information and the inability to store genomic information in current EHR systems.
Integrating genomic medicine into primary care in Canada involves family physician questionnaires, which reveal a lack of confidence in genomic medicine skills needed for practice and cautious optimism about its clinical benefits.
Family physicians in Canada see their role in developing family history/pedigrees, making referrals, and supporting patients with genetic diseases, but they need training and educational resources that can be integrated into primary care practice.
Educational resources for primary care practice in genomic medicine should include case studies starting with the first presentation of the patient in the primary care setting.
The study is authored by Dr. Darl Ray Swartz and published in npj Genomic Medicine (2020) and Frontiers in Genetics.

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Description

Explore the genomic changes associated with aging and undiagnosed diseases, including insights into decline in mitochondrial number, somatic variant burden, and diagnostic methods. Delve into the integration of genomic medicine into healthcare, covering analytical methods, insurance challenges, EHR integration, and the role of primary care physicians. Authored by Dr. Darl Ray Swartz, this study provides valuable insights into the evolving landscape of genomic medicine.