genomics

Two promises of genomic healthcare

- Better understanding of the molecular mechanisms of disease - Care that is individualized based on genomic differences--now called "Precision Medicine"

To care for persons/families/ communities and/or populations throughout the life span, registered nurses will need to

-demonstrate proficiency with incorporating genetic and genomic information into their practice. -Understand the genetic and genomic basis of health and/or an illness for which the person is seeking care and the variables that impact his or her response. • Recognize a newborn at risk for morbidity or mortality resulting from genetic metabolism errors. • Identify an asymptomatic adolescent who is at high risk for hereditary colon cancer. • Identify a couple at risk for having a child with a genetic condition. • Guide interventions for the prevention of cardiovascular disease in young adults. -Facilitate drug selection or dosage in treatment of an adult with cancer based on molecular markers. • Promote informed consent that includes the risks, benefits, and limitations of participation in genetic research. • Assist anyone having questions about genetic and genomic information or services. • Identify Caucasians of northern European descent (a population at risk for hemachromatosis) who have joint disease, severe and continuing fatigue, heart disease, elevated liver enzymes, impotence, and diabetes, because they are candidates for hemochromatosis HFE genetic testing.

how many pairs of bases in genome

3 billion

how many bases in genome

6 billions

percentage of the population caring gene is common when it's

>1%

DNA mutation

A gene mutation is a permanent alteration in the DNA sequence that makes up a gene, such that the sequence differs from what is found in most people. Mutations range in size; they can affect anywhere from a single DNA building block (base pair) to a large segment of a chromosome that includes multiple genes.

Mutation

A mutation is a change in a DNA sequence. Mutations can result from DNA copying mistakes made during cell division, exposure to ionizing radiation, exposure to chemicals called mutagens, or infection by viruses. Germ line mutations occur in the eggs and sperm and can be passed on to offspring, while somatic mutations occur in body cells and are not passed on.

What is the nurses' role in precision healthcare?

Advocacy, Protection, Education Anticipatory guidance Surveillance Taking action Effective communication Patient education

base pair

At GC a pair of complementary bases in a double-stranded nucleic acid molecule, consisting of a purine in one strand linked by hydrogen bonds to a pyrimidine in the other. Cytosine always pairs with guanine, and adenine with thymine (in DNA) or uracil (in RNA).

Dual role of BSN-prepared nurses

Caring for and protecting patients Informed citizens in a global society

cell

Cells are the basic building blocks of all living things. The human body is composed of trillions of cells. They provide structure for the body, take in nutrients from food, convert those nutrients into energy, and carry out specialized functions. Cells also contain the body's hereditary material and can make copies of themselves. Cells have many parts, each with a different function. Some of these parts, called organelles, are specialized structures that perform certain tasks within the cell.

complex or multifactorial disorder

Conditions caused by many contributing factors. do not have a single genetic cause—they are likely associated with the effects of multiple genes in combination with lifestyle and environmental factors. heart disease, diabetes, and obesity

chromosome structure

DNA +Protein packaging(histone) Three parts LONG ARM< SHORT ARM AND CENTROMERE 23 pairs, autosomes and sex

Gene number disfunction example

Down syndrome

DNA hybridization

FishHeat to separate strands Add identical Dna with attached probes Cool to allow renaturation of double stranded DNA

protein syntesis

From this strand the protein will be synthesized, this is called translation (RNA is translated into protein). A protein is made from amino acids, these form a strand. ... The translation of RNA to protein is different than the synthesis of RNA from DNA (transcription).

Gene can be dysfunctional can be related to

Gene structure - sequence Gene function - expression Gene number or dose - wrong amount of DNA

transcription

In transcription, the DNA sequence of a gene is transcribed (copied out) to make an RNA molecule.

protein

Large molecules composed of one or more chains of amino acids in a specific order determined by the base sequence of nucleotides in the DNA coding for the protein. Proteins are required for the structure, function, and regulation of the body's cells, tissues, and organs.

DNA

Linear structure, nDNA and mtDNA

Mitochondria

Mitochondria are complex organelles that convert energy from food into a form that the cell can use. They have their own genetic material, separate from the DNA in the nucleus, and can make copies of themselves

haploid

One chromosome set 3 billion base pairs

chromosome

Organized 'package' of DNA in the cell nucleus Uncoiled most of the time (interphase) Condensed and visible (metaphase) single long DNA molecule. Portion of gene. Structure housing DNA. Entire cell 23 pairs with 22 numbered. Found in nucleus. Each parent gives one chromosome for each pair.

Mendelian

Single gene inheritance law patterns of inheritance that are characteristic of organisms that reproduce sexually. The Austrian monk Gregor Mendel performed thousands of crosses with garden peas at his monastery during the middle of the 19th century. Mendel explained his results by describing two laws of inheritance that introduced the idea of dominant and recessive genes. Did not consider variations in gene expression Had a large role in the health care of a few, and a small role in the health care for many

Genomics

Study of all the genes in the human genome together, including their interactions with each other, the environment, and the influence of other psychosocial and cultural factors

Genetic

Study of individual genes and their impact on relatively rare single gene disorders

Golgi apparatus

The Golgi apparatus packages molecules processed by the endoplasmic reticulum to be transported out of the cell.

centromere

The centromere is the part of a chromosome that links sister chromatids or a dyad. During mitosis, spindle fibers attach to the centromere via the kinetochore.

Cytoskeleton

The cytoskeleton is a network of long fibers that make up the cell's structural framework. The cytoskeleton has several critical functions, including determining cell shape, participating in cell division, and allowing cells to move. It also provides a track-like system that directs the movement of organelles and other substances within cells.

competencies were developed on the basis of:

The results of a review of peer-reviewed published work reporting practice-based genetic and genomic competencies, guidelines, and recommendations. • Input from nurse representatives to the National Coalition for Health Professional Education in Genetics (NCHPEG) meeting in January, 2005. • Public comment from the nursing community at large. • Statements from conference attendees during open comment periods during a two-day meeting of key stakeholders (listed on pages 3 and 4) held September 21 and 22, 2005

Lysosomes and peroxisomes

These organelles are the recycling center of the cell. They digest foreign bacteria that invade the cell, rid the cell of toxic substances, and recycle worn-out cell components

Endoplasmic reticulum (ER)

This organelle helps process molecules created by the cell. The endoplasmic reticulum also transports these molecules to their specific destinations either inside or outside the cell.

Translation

Translation is the final step on the way from DNA to protein. It is the synthesis of proteins directed by a mRNA template. The information contained in the nucleotide sequence of the mRNA is read as three letter words (triplets), called codons

diploid

Two chromosome sets 6 billion base pairs

Purpose of genomics

Understanding molecular mechanisms r/t gene function in health and disease - where/how can we intervene?

Cytoplasm

Within cells, the cytoplasm is made up of a jelly-like fluid (called the cytosol) and other structures that surround the nucleus.

exon

a segment of a DNA or RNA molecule containing information coding for a protein or peptide sequence.

intron

a segment of a DNA or RNA molecule that does not code for proteins and interrupts the sequence of genes.

hydrogen bond

a weak bond between two molecules resulting from an electrostatic attraction between a proton in one molecule and an electronegative atom in the other.

human genome

all the gene of human being

precision medicine

an emerging approach for disease treatment and prevention that takes into account individual variability in genes, environment, and lifestyle for each person

histone

any of a group of basic proteins found in chromatin.

autosome

any of the numbered chromosomes. Numbered in relations to size. more the size smaller the number

nucleotide

base, sugar, and phosphate are called a nucleotide a compound consisting of a nucleoside linked to a phosphate group. Nucleotides form the basic structural unit of nucleic acids such as DNA.

Definition of gene 1908

basic physical and functional unit of heredity

Gene function disfunction example

breast and ovarian cancer, schizophrenia

Precision Medicine Initiative long tearm goal

bringing precision medicine to all areas of health and healthcare on a large scale.

surveillance

close observation

genome

complete set of DNA, including all of its genes. Each genome contains all of the information needed to build and maintain that organism. In humans, a copy of the entire genome—more than 3 billion DNA base pairs—is contained in all cells that have a nucleus.

Moore's law in genomics

cost per genome fell from 100M in 2001 to 1K in 2015

Genomic diseases and conditions caused by

cumulative effects of multiple genes and the environment

gene

distinct sequence of nucleotides forming part of a chromosome, the order of which determines the order of monomers in a polypeptide or nucleic acid molecule which a cell (or virus) may synthesize.functional, structural piece. basic physical unit of inheritance contains info to specify traits, Arranged one after another in a structure called chromosome. Chromosome contains single long DNA only portion of which contains single long DNA molecule. Humans have about 20K gene arranged on chromosome.

All of us

effort to gather data from one million or more people living in the United States to accelerate research and improve health. By taking into account individual differences in lifestyle, environment, and biology, researchers will uncover paths toward delivering precision medicine.

DNA use of fluorescent probes

fragment of DNA or RNA of variable length (usually 100-1000 bases long) which can be radioactively labeled. It can then be used in DNA or RNA samples to detect the presence of nucleotide sequences (the DNA target) that are complementary to the sequence in the probe.

heterozygous

functionally different

homozygotus

functionally same

1970 idea of genes

gene is the blueprint for making proteins. one gene makes one enzyme

GWAS

genome-wide association study or whole genome association study (WGA study, or WGAS), is an examination of a genome-wide set of genetic variants in different individuals to see if any variant is associated with a trait.

Hap Map

haplotype map (HapMap) of the human genome, to describe the common patterns of human genetic variation. HapMap is used to find genetic variants affecting health, disease and responses to drugs and environmental factors.

Precision Medicine Initiative

how a person's genetics, environment, and lifestyle can help determine how best to prevent or treat disease. long-term research

DNA VARIANT

ingle nucleotide polymorphisms ("SNPs", pronounced "snips") are DNA sequence variations that occur when a single nucleotide differs from the reference DNA sequence. Insertions are when additional nucleotides inserted in a DNA sequence, relative to the reference sequence. Deletions are when there are missing nucleotides, relative to the reference sequence. Substitutions are when multiple nucleotides are altered from the reference sequence. Structural variants are changes where large sections of a chromosome or even whole chromosomes are duplicated, deleted or rearranged in some manner.

human genome project

international project that mapped and sequenced the entire human genome. Completed in April 2003, data from the project are freely available to researchers and others interested in genetics and human health.

Human Genome Project

international research effort to determine the sequence of the human genome and identify the genes that it contains. allowed researchers to begin to understand the blueprint for building a person. As researchers learn more about the functions of genes and proteins, this knowledge will have a major impact in the fields of medicine, biotechnology, and the life sciences. -to provide a complete and accurate sequence of the 3 billion DNA base pairs that make up the human genome and to find all of the estimated 20,000 to 25,000 human genes. The Project also aimed to sequence the genomes of several other organisms that are important to medical research, such as the mouse and the fruit fly. -to develop new tools to obtain and analyze the data and to make this information widely available. Also, because advances in genetics have consequences for individuals and society, the Human Genome Project committed to exploring the consequences of genomic research through its Ethical, Legal, and Social Implications (ELSI) program. -to identify which genes are critical for life.

1000 genomes

international research effort to establish by far the most detailed catalogue of human genetic variation. Scientists planned to sequence the genomes of 2500 participants from a 50 different populations to find common variances with frequency of >1% . Many rare variations, restricted to closely related groups, were identified, and eight structural-variation classes were analyzed

Precision Medicine Initiative short tearm goal

involve expanding precision medicine in the area of cancer research. Researchers at the National Cancer Institute (NCI; the NIH institute focused on cancer research) hope to use this approach to find new, more effective treatments for various kinds of cancer based on increased knowledge of the genetics and biology of the disease.

locus

location(address) of gene on the chromosome

percision medicine initiative

long-term research endeavor, involving the National Institutes of Health (NIH) and multiple other research centers, which aims to understand how a person's genetics, environment, and lifestyle can help determine how best to prevent or treat disease.

null allele

mutant copy of a gene at a locus that completely lacks that gene's normal function. This can be the result of the complete absence of the gene product (protein, RNA) at the molecular level, or the expression of a non-functional gene product.

Genetic diseases caused by

mutation/disfunction in a single gene

base

nitrogen-containing biological compounds that form nucleosides, which in turn are components of nucleotides; all which are monomers that are the basic building blocks of nucleic acids.

precision medicine vs personalized medicine?

older term with a meaning similar to "precision medicine." However, there was concern that the word "personalized" could be misinterpreted to imply that treatments and preventions are being developed uniquely for each individual; in precision medicine, the focus is on identifying which approaches will be effective for which patients based on genetic, environmental, and lifestyle factors

allele

one or more versions of gene. An individual inherits two alleles for each gene. If alleles are different person is heterozygous, if same homozygous. IT is variation among noncoding DNAsequenses

sex chromosome

participates in sex determination. 2 X and Y. Female has X and X, Male has X andY. So male is responcible for sex of a baby

metaphase

preparing to divide. Chromosomes are visible at this phase when condinsed

Anticipatory guidance

proactive developmentally based counseling technique that focuses on the needs of a patient A particular kind of advocacy

DNA replication

process of producing two identical replicas of DNA from one original DNA molecule.

gene promoter

region of DNA that initiates transcription of a particular gene. Promoters are located near the transcription start sites of genes, on the same strand and upstream on the DNA (towards the 5' region of the sense strand).

alternative splicing

regulated process during gene expression that results in a single gene coding for multiple proteins. In this process, particular exons of a gene may be included within or excluded from the final, processed messenger RNA (mRNA) produced from that gene.

monogenic disorder

result of the single defective gene of autosome. Mendelian law. It can be spontaneous with no previous history

copy number variant

sections of the genome are repeated and the number of repeats in the genome varies between individuals in the human population.

Gene

sequence of nucleotides on the chromosome

how different are humans from each other

share >99% of DNA sequence. Mitochondrial are more variable

Gene structure disfunction example

sickle cell anemia, cystic fibrosis

monogenic

single gene

mRNA (transcript)

single-stranded ribonucleic acid (RNA) product synthesized by transcription of DNA, and processed to yield various mature RNA products such as mRNAs, tRNAs, and rRNAs. The primary transcripts designated to be mRNAs are modified in preparation for translation.

epigenetic effects

study of heritable changes in gene expression (active versus inactive genes) that does not involve changes to the underlying DNA sequence — a change in phenotype without a change in genotype — which in turn affects how cells read the genes.

Pharmacogenomics

study of how genes affect a person's response to particular drugs. Part of precision medicine

chromatin

the material of which the chromosomes of organisms other than bacteria (i.e., eukaryotes) are composed. It consists of protein, RNA, and DNA.

karyotype

the number and visual appearance of the chromosomes in the cell nuclei of an organism or species.individual's collection of chromosomes. The term also refers to a laboratory technique that produces an image of an individual's chromosomes. The karyotype is used to look for abnormal numbers or structures of chromosomes. NUMBER, SEX with letters NUMBER< SEX WITH LETTERS, +21

eugenics

the science of improving a human population by controlled breeding to increase the occurrence of desirable heritable characteristics. Developed largely by Francis Galton

What were some of the ethical, legal, and social implications addressed by the Human Genome Project?

to identify and address issues raised by genomic research that would affect individuals, families, and society

gene expression

transcription/translation "the software" Whether / to what degree gene is 'turned on' (being transcribed) Varies widely among tissues Regulated by other genes, intergenic DNA, and epigenetic effects

central dogma

two-step process, transcription and translation, by which the information in genes flows into proteins: DNA → RNA → protein. Transcription is the synthesis of an RNA copy of a segment of DNA.

wild type

typical form of a species as it occurs in nature. Originally, the wild type was conceptualized as a product of the standard "normal" allele at a locus, in contrast to that produced by a non-standard, "mutant" allele.

Personalized health care P4

used to describe a systems approach to medicine that includes predictive, personalized, preventive and participatory aspects.

interphase

working

Potential benefits of the Precision Medicine Initiative:

• New approaches for protecting research participants, particularly patient privacy and the confidentiality of their data. • Design of new tools for building, analyzing, and sharing large sets of medical data. • Improvement of FDA oversight of tests, drugs, and other technologies to support innovation while ensuring that these products are safe and effective. • New partnerships of scientists in a wide range of specialties, as well as people from the patient advocacy community, universities, pharmaceutical companies, and others. • Opportunity for a million people to contribute to the advancement of scientific research.

Potential long-term benefits of research in precision medicine:

• Wider ability of doctors to use patients' genetic and other molecular information as part of routine medical care. • Improved ability to predict which treatments will work best for specific patients. • Better understanding of the underlying mechanisms by which various diseases occur. • Improved approaches to preventing, diagnosing, and treating a wide range of diseases. • Better integration of electronic health records (EHRs) in patient care, which will allow doctors and researchers to access medical data more easily.