A genetic predisposition is a genetic characteristic which influences the possible phenotypic development of an individual organism within a species or population under the influence of environmental conditions. In medicine, genetic susceptibility to a disease refers to a genetic predisposition to a health problem,[1] which may eventually be triggered by particular environmental or lifestyle factors, such as tobacco smoking or diet. Genetic testing is able to identify individuals who are genetically predisposed to certain diseases.

Predisposition is the capacity we are born with to learn things such as language and concept of self. Negative environmental influences may block the predisposition (ability) we have to do some things. Behaviors displayed by animals can be influenced by genetic predispositions. Genetic predisposition towards certain human behaviors is scientifically investigated by attempts to identify patterns of human behavior that seem to be invariant over long periods of time and in very different cultures.

For example, philosopher Daniel Dennett has proposed that humans are genetically predisposed to have a theory of mind because there has been evolutionary selection for the human ability to adopt the intentional stance.[1] The intentional stance is a useful behavioral strategy by which humans assume that others have minds like their own. This assumption allows you to predict the behavior of others based on personal knowledge of what you would do.

E. O. Wilson's book on sociobiology and his book Consilience discuss the idea of genetic predisposition to behaviors

The field of evolutionary psychology explores the idea that certain behaviors have been selected for during the course of evolution.

The Genetic Information Nondiscrimination Act, which was signed into law by President Bush on May 21, 2008,[2] prohibits discrimination in employment and health insurance based on genetic information.

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Genetic predisposition - Wikipedia

On Saturday, Sept. 16, Baylor College of Medicine will bring a community conference and resource fair to the Midland area to provide an educational seminar and support materials for children with special needs, as well as their parents.

Provided jointly by Baylor and Texas Childrens Hospital, in collaboration with SHARE West Texas, the conference will address the role genetic evaluations play in patients with autism spectrum disorders.

Dr. Daryl Scott, associate professor of molecular and human genetics at Baylor, will walk parents through the steps of a genetic evaluation and discuss what the findings mean, citing relevant case studies. The emphasis will be placed on common causes of autism, including Fragile X syndrome, chromosomal abnormalities and mutations affecting genes linked to autism.

Conference attendees will learn how new genetic tests have made it possible to determine why some children are affected by autism spectrum disorders. When a specific case is identified, it allows physicians to provide accurate counseling and improved medical care for all family members, Scott said.

The resource fair will offer current information on care, education and research as they relate to autism spectrum disorders and encourages networking within the community by connecting patients and their families with others in similar situations.

Our goal in introducing this program to the Midland community is to broaden the awareness of these disorders while also providing parents and families with the knowledge and resources they need to cope with the behavioral and developmental disabilities that often accompany them, said Susan Fernbach, director of genetic outreach at Baylor and Texas Childrens.

The program is free and open to the public, but registration is required. The seminar will be held at Midland Shared Spaces, at 3500 North A St. To register, email Traci Hopper at thopper@sharewtx.org, or call 432-818-1259. The resource fair begins at 9 am, and the conference will follow at 10 am. Lunch will be provided.

This conference is supported by the Texas Center for Disability Studies at the University of Texas at Austin and the Texas Department of State Health Services.

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Midland to host community conference for genetic conditions - Baylor College of Medicine News (press release)

James N. Jarvis, MD, is conducting a study of the gene-environment paradigm for juvenile idiopathic arthritis pathogenesis.

Published August 14, 2017

JamesN. Jarvis, MD, clinical professor of pediatrics, will usean Arthritis Foundationgrant to study how genes and environment work together to influencethe immune dysfunction in juvenile arthritis.

After asthma, juvenile idiopathic arthritis (JIA) is the mostcommon chronic disease condition in children. While genetics play asmall role in the disease, environmental factors are also known tobe important.

Study Focuses on Influence of Epigenome

The study, titled Interplay Between Genetics andEpigenetics in Polyarticular JIA, builds upon previous workby Jarvis and his fellow researchers.

The epigenome refers to the features of DNA and the proteinsthat DNA is wrapped around that do not control the genetic makeupof a person but do influence how cells respond to the environment,says Jarvis, principal investigator on the grant.

Specifically, the epigenome determines what genes a cellwill turn on or turn off in response to environmental cues,he notes.

New Paradigm of Pathogenesis Informs Research

Like most complex traits, genetic risk for JIA is principallylocated within non-coding regions of the genome.

Our preliminary studies present the hope that we canfinally understand the gene-environment paradigm forJIA pathogenesis, Jarvis says.

Rather than regarding JIA as an autoimmunedisease, triggered by inappropriate recognition of aself protein by the adaptive immune system, Jarvishypothesizes that JIA emerges because leukocytes suffer geneticallyand epigenetically mediated perturbations that blunt their capacityto regulate and coordinate transcriptions across the genome.

This loss of coordinate regulation leads to inappropriateexpression of inflammatory mediators in the absence of the normalexternal signals typically required to initiate or sustain aninflammatory response, he says.

Our field has been dominated by a single hypothesis forJIA pathogenesis for 30 years, Jarvis notes. However,as the field of functional genomics becomes increasingly wedded tothe field of therapeutics, our work carries the promise ofcompletely new approaches to therapy based on a completelydifferent paradigm of pathogenesis.

Newly Diagnosed Children Tested in Study

The researchers are recruiting 30 children with newly diagnosedpolyarticular JIA for its study to survey the epigenome and CD4+ Tcells in them and compare the results with findings in 30 healthychildren.

We plan to build a multidimensional genomic map thatsurveys the functional epigenome, examines underlying geneticvariation and examines the effects of genetic and epigeneticvariation on gene expression, Jarvis says.

He notes the work will focus on CD4+ T cells because theresearchers have already identified interesting interactionsbetween their epigenome and transcriptome in the context oftherapeutic response in JIA.

Taking Novel Approach to Understanding Disease

Because the epigenome is the medium through which theenvironment exerts its effects on cells, Jarvis believes thatcharacterizing the epigenome in pathologically relevant cells,ascertaining where epigenetic change is linked to genetic variationand determining how genetic and epigenetic features of the genomeregulate or alter transcription is the key to truly understandingthis disease.

This project addresses a question that parents alwaysask, which I never thought wed begin to answer in mylifetime: What causes JIA? This study wontprovide the whole answer, but it will go a long way toward takingus there, he says.

The project has three specific aims:

Arthritis Patients Help Determine Funded Projects

The two-year, $730,998 grant is part of the ArthritisFoundations 2016 Delivering on Discovery awards. It was oneof only six projects out of 159 proposals chosen for funding. Forthe first time, arthritis patients helped the foundation selectprojects.

Including patient input as part of the selection processwas a new milestone in patient engagement for the ArthritisFoundation and allowed us to select projects that hold the mostpromise from an arthritis patients point of view,says Guy Eakin, senior vice president, scientific strategy.

Partners from JSMBS, Philadelphia Hospital

Collaborators from the JacobsSchool of Medicine and Biomedical Sciences are:

Other collaborators include researchers from theChildrens Hospital of Philadelphia.

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Studying How Genes, Environment Contribute to Juvenile Arthritis - UB School of Medicine and Biomedical Sciences News

Using fragments of circulating tumor DNA in blood, University of California San Diego School of Medicine researchers were able to identify theoretically targetable genetic alterations in 66 percent of patients with cancer of unknown primary (CUP), a rare disease with seven to 12 cases per 100,000 people each year.

In order to plan treatment for cancer in general, physicians first attempt to pinpoint the primary cancer where the tumor first developed. In CUP, despite its spread throughout the body, the origin remains unknown, making treatment more difficult. The current standard of care is platinum-based combination chemotherapies with a median survival time of six to eight months.

Razelle Kurzrock, MD, director of the Center for Personalized Cancer Therapy at Moores Cancer Center at UC San Diego Health.

In a study published in the journal Cancer Research on August 15, researchers report that by sequencing circulating tumor DNA (ctDNA) derived from blood samples in 442 patients with CUP, they were able to identify at least one genetic alteration linked to cancer in 290 66 percent of patients. Researchers used a screening test developed by Guardant Health that evaluates up to 70 genes. Based on known carcinogenic mutations, 99.7 percent of the 290 patients who had detectable tumor DNA in their bloodstream had genomic alterations that could hypothetically be targeted using existing FDA-approved drugs (as off-label use) or with therapies currently under investigation in clinical trials.

By definition, CUP does not have a definite anatomical diagnosis, but we believe genomics is the diagnosis, said Razelle Kurzrock, MD, director of the Center for Personalized Cancer Therapy at Moores Cancer Center at UC San Diego Health and senior author. Cancer is not simple and CUP makes finding the right therapy even more difficult. There are multiple genes and abnormalities involved in different areas of the body. Our research is the first to show that evaluating circulating tumor DNA from a tube of blood is possible in patients with CUP and that most patients harbor unique and targetable alterations.

A blood or liquid biopsy is a diagnostic tool based on the idea that critical genetic information about the state of disease can be found in blood or other fluids. One vial of blood could be used to detect the onset of disease, monitor its progression and measure its retreat less invasively than a tissue biopsy.

Shumei Kato, MD, assistant professor of medicine at UC San Diego School of Medicine.

Another advantage of the liquid biopsy is that the location of the cancer does not matter, said Shumei Kato, MD, assistant professor of medicine at UC San Diego School of Medicine and first author. With a blood sample, we can analyze the DNA of tumors throughout the body to find targetable alterations. With tissue biopsies, we can only see genomic changes that are in that one site and that may not be the same as what is in different sites not biopsied, such as the lung or bone.

Liquid biopsies are relatively simple to get and can be obtained regularly to monitor changes over time, as was the case with a 60-year-old woman with CUP. Her case, which was evaluated by Brian Leyland-Jones, MB, BS, PhD and study co-author with colleagues at Avera Cancer Institute, was described in the study to show the changes observed in ctDNA over the course of her treatment.

What we saw was that the patient was responding to treatment, but the cancer had emerging new mutations, said Kurzrock. Whats new here is that we can do the same evaluation through a blood test that we previously could only do with a tissue sample. You will see these changes with a simple blood test and it is easy to repeat blood tests, but hard to repeat tissue biopsies.

The study also reported the case of an 82-year-old man who was prescribed a checkpoint inhibitor immunotherapy as part of his treatment because of a mismatch repair gene anomaly that is typically observed in less than two percent of patients. He showed a partial response within eight weeks and blood biopsies showed the tumor DNA disappearing.

We can see that each patient has different mutations in their tumor DNA, which means that treatment plans cannot be a one-size-fits-all approach; a personalized approach is needed, said Kato.

Kurzrock is already using liquid biopsy technology in the Profile Related Evidence Determining Individualized Cancer Therapy (PREDICT) clinical trial a project focusing on the outcome of patients who have genomic testing performed on their tumors and are treated with targeted therapy.

The authors suggest that a liquid biopsy approach should be further investigated in next-generation clinical trials focusing on CUP.

Co-authors include: Nithya Krishnamurthy, Scott M. Lippman, UC San Diego; Kimberly C. Banks, Richard B. Lanman, Guardant Health, Inc.; Pradip De, Kirstin Williams, and Casey Williams, Avera Cancer Institute.

This research was funded, in part, by the National Cancer Institute (P30 CA016672) and the Joan and Irwin Jacobs fund.

Disclosure: Razelle Kurzrock receives consultant fees from X-biotech and from Actuate Therapeutics, as well as research funds from Genentech, Pfizer, Sequenom, Guardant, Foundation Medicine and Merck Serono, and has an ownership interest in Novena Inc. and CureMatch Inc.

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Blood Biopsy Reveals Unique, Targetable Genetic Alterations in Patients with Rare Cancer - UC San Diego Health

After years of fanfare and a few false starts, the era of genomic medicine has finally arrived.

Across the country, thousands of patients are being treated, or having their treatment changed, based on information gleaned from their genome. Its a revolution that has been promised since the human genome was first published in 2001. But making it real required advances in information technologyinfrastructure and a precipitous drop in price.

Today, the cost of whole exome sequencing, which reveals the entire protein-coding portion of DNA, is now roughly equivalent to an MRI exam in many parts of the country, says Louanne Hudgins, M.D., president of the American College of Medical Genetics and Genomics and director of perinatal genetics at Lucile Packard Children'sHospital Stanford, Palo Alto, Calif.

Genomic sequencing is a tool like any other tool in medicine, and its a noninvasive tool that continues to provide useful information for years after it is performed, she says.

Nowhere is this genomic transformation more apparent than in the realm of cancer treatment.

Companies like Menlo Park, Calif.-based Grail Inc. are forging ahead with large-scale genomic sequencing projects in collaboration with both academic medical centers and community health systems. Grails Circulating Cell-free Genome Atlas study aims to identify genomic fingerprints shed from tumors that can be identified in a blood sample. The goal is to help identifycancers early when they are more treatable and to match a patients tumors to individualized treatment.

We are finding great enthusiasmas people want to participate in this effort, both patients and physicians, says Mark Lee, M.D., a practicing oncologist at Stanford and head of clinical development and medical affairs at Grail. Right now, he says, health systems and patients have an opportunity to participate in shaping the future of this genome-based medicine.

Supporting article:Maine Genomics Project Rethinks Cancer Care

Backed by investing giants like Amazon and Bill Gates, Grail has partnered with the Mayo Clinic, the Cleveland Clinic, the U.S. Oncology Networkand others to collect de-identified data from consenting patients for large-scale genomic studies.

And they have lots of company. The biotech company Regeneron has partnered with Pennsylvania-based Geisinger Health System to enroll interested patients in a project dubbed MyCode Community Health Initiative. A discovery-focused initiative, MyCode is also using genomic data to guide treatment decisions today. Currently, the project has enrolled more than 150,000 consenting patients and has returned what are considered actionable results to 340 patients and providersand counting.

For example, MyCode participant Barbara Barnes chose to have her reproductive organs removed after an analysis of her DNA determined that she was at increased risk for developing breast and ovarian cancer. The surgeryrevealed that she already had a fallopian tube tumor that required treatment, and the early intervention may have saved her life. She shared her story in a Facebook video produced by Geisinger.

While anecdotal success stories provide a taste of whats possible, the Geisinger-Regeneron collaboration is aimed more toward matching genotypes with treatment on a population level, and that effort is starting to yield results.

In July, the group published a report in the New England Journal of Medicine describing a variant of the gene ANGPTL3 associated with a reduced risk of cardiovascular disease detected in some MyCode participants. The gene variant codes for a protein that seems to lower cholesterol, and the company has developed a targeted treatment, evinacumab, that mimics the action of this protein. Evinacumab earned breakthrough therapy designation by the Food and Drug Administrationin April and is now in Phase 3 clinical trials for patients with an inherited tendency that manifests early in life to have high cholesterol levels, leading to deadly cardiovascular disease.

Another goal of Geisingers population-based study, says Andy Faucett, a principal investigator of MyCode and genomics researcher at Geisinger, is to determine how to scale the program and make it possible for more health systems to implement genomic screening for their patients.

We probably have a health system a week call us and ask us for help [setting up a genomics program], he says. We think its something that should be offered to every patient.

Genomic medicine has advanced to the point that genes and their variants now can be targets for drug treatments. Case in point: In May, the FDA approved pembrolizumab (Keytruda) to treat any unresectable or metastatic solid tumor with a specific genetic biomarker, irrespective of its location in the body.

This is an important first for the cancer community, Richard Pazdur, M.D., director of the FDA's Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products in the FDAs Center for Drug Evaluation and Research, said in a statement made at the time of the approval. We have now approved a drug based on a tumors biomarker without regard to the tumors original location.

Clinical trials matching genomic markers with targeted treatment are well underway and are only expected to increase, making identification of genomic targets an essential part of care.

Targeted therapies got another advance in July when an advisory panel convened by the FDA gave its unanimous recommendation for approval of the first gene-based medical treatment in the U.S. Chimeric antigen receptor T, or CAR-T,cell therapy, expected to be approved in November for a particularly aggressive form of leukemia, is the first in a wave of living drugs engineered to seek out and destroy cancerous tumors.

CAR-T cell therapy represents the culmination of decades of research to identify genetic features that are unique to each specific form of cancer that can be targeted by the immune system. The approach, coaxing a patients own immune system to recognize and attack cancerous cells, also delivers on the promise of personalized medicine, as T cells are harvested from each patient, re-engineered to recognize and attack cancer, and returned to the patient.

In the case of Novartis CTL019, the treatment on the cusp of FDA approval, complete response rates in clinical trials for acute lymphoblastic leukemia patients whohad relapsed despite multiple conventional treatments, reached 80-90%.

Physician-scientists like Brian Till of Seattles Fred Hutchinson Cancer Research Center, who has been working on CAR-T for years but was not involved in the development of CTL019, say these early results are encouraging.

We have enough data right now to be optimistic that this could become standard of care for some cancers, says Till.

He quickly added that there will likely always be a role for chemotherapy or other standard treatments and that CAR-T will probably be limited in its early days to centers that have experience managing potential toxicities. But, he added, CAR-T has the potential to be given as an outpatient treatment with careful management of side effects.

Many questions remain about whether it makes sense for healthy people to learn the secrets hidden in their DNA, but those concerns are likely to be overshadowed by a cavalcade of genomic sequencing projects and targeted therapies now hitting clinics nationwide. Simply put, genomic sequencing will be part of standard care within the next decade.

In the realm of rare-disease diagnoses and treatment, genomics already has been transformative. As recently as five years ago, patients with myriad vague symptoms, mostly infants and children, could bounce from doctor to doctor and invasive procedure to invasive procedure without ever receiving a definitive diagnosis. While some disorders still do evade diagnosis, whole genome sequencing has dramatically reduced that number.

Our ability to diagnose genetic conditions has improved dramatically, says Hudgins. And we are gaining a much better understanding of the biology behind these genetic changes. Because of these advances, therapy and management of these diseases are much improved. So the idea that there is no treatment for genetic disorders is just not true anymore.

The speed of DNA sequencing and analysis now permits near real-time diagnosis, moving it into the clinical workflow.

At Rady Childrens HospitalSan Diego, an array of Illumina sequencing machines churns through clinical samples in as few as 37 hours, according to Stephen Kingsmore, M.D., director of its Institute forGenomic Medicine.

The rapid sequence analysis has resulted in almost half of patients receiving a genomic diagnosis, while 80 percent had their care altered as a result of sequencing.

Kingsmore is consulting with a dozen other childrens hospitals that want to offer real-time genomic testing to their patients within the next year. Every hospital should have access to rapid sequencing and analysis within a few years, he says.

For prospective parents, prenatal and perinatal diagnosis has entered a new realm as well.

Cell-free DNA prenatal screening has dramatically decreased the number of invasive procedures such as amniocentesis and chorionic villus sampling that pregnant women undergo, Hudgins says. In the last few years, it has decreased fivefold in many areas of the U.S.

Even the granddaddy of all genomic medicine, gene therapy, is enjoying a renaissance. Early efforts to treat disease by replacing defective genes suffered many setbacks over the years, mainly due to the difficulty of efficiently delivering genes to affected tissues and organs. But next-generation modified viral delivery systems have shown they can get the job done safely and efficiently.

Philadelphia-based Spark Therapeutics' biologics license application for voretigene neparvovec (Luxturna)for inherited retinal disease has been accepted for review by the FDA with a decision expected early next year. The experimental treatment of 31 patients was the first successful randomized, controlled Phase 3gene therapy clinical trial, leading to FDA orphan drug designation in July.

Spark is one of several companies developing gene-based treatment for vision loss in the U.S. and Europe.

Similarly, Bluebird Bio Inc.'s gene-therapy treatment for thalassemia and sickle cell disease has shown promise. Results presented at the European Hematology Association meeting in Vienna in June suggested that a child treated for severe sickle cell disease in France might have been cured.

The company is running clinical trials to treat severe sickle cell disease at six hospitals in the U.S., including the Medical University of South Carolina. Julie Kanter, M.D., director of sickle cell research at MUSC and a primary investigator on the U.S. trial, says the new generation of gene-delivery systems is more efficient with fewer side effects.

I think weve made incredible headway and we are going to see some great things coming, she says.

Amid tumbling genomic sequencing costs, more people are having their DNA sequenced to match an underlying genetic defect withan increasing variety of targeted treatment options. From an estimated 1,000 genetic tests available only five years ago, the field has exploded to more than 52,000 available in the U.S., and that number grows daily. To find out more about what's out there, visit the National Center for Biotechnology Information's Genetic Testing Registry website at http://www.ncbi.nlm.nih.gov/gtr.

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Genomic Medicine Has Entered the Building - Hospitals & Health Networks