Basic Concepts of Personalized Medicine Flashcards
How many cells are in the human body?
30-40 trillion
How many different types of cells are in the human body?
over 200 different types
-such as neurons, epithelial cells, RBCs
How many cells die each day?
100 billion
-replaced by new cells by cell division
-each division is called a “cell cycle”
What are the phases of the cell cycle?
G1 (gap 1): cell grows and prepares for DNA replication
S (synthesis): DNA replication
G2 (gap 2): cell continues to grow and prepare for mitosis
M (mitosis): cell stops growth and starts division
G0 (gap 0): cell has left the cell cycle and stopped dividing
What are the checkpoints in the cell cycle?
G1 and G2
-apoptosis starts if anything goes wrong
-G1 checkpoint: DNA synthesis
-G2 checkpoint: preparation for mitosis
What is R (restriction point) of the cell cycle?
cell has committed to the cycle for division
How many pairs of chromosomes are in the human body?
23 pairs
-complex of a DNA molecule and proteins
What is the structure of a DNA molecule?
linear double-stranded (50-250 million base pairs)
How many genes are within the average chromosome?
average chromosome contains 2500-5000 genes within 130 million base pairs
Are genes evenly distributed on a chromosome?
no, could be clustered
-microband (3-5 million base pairs and 60-120 genes)
What percentage of human chromosomes code for genes? What is the role of the rest of the human chromosomes?
10% code for genes
rest play regulating role
What is a gene?
a portion of chromosomal DNA sequence required for the production of a protein or a functional RNA molecule
-include the coding sequence and adjacent sequence required for regulation of expression (such as promoters)
What is the size of a gene?
varies
-small (1.5 kb) or large (2000 kb)
What is RNA splicing?
precursor mRNA –> mRNA
What are the four types of nucleotides in DNA?
A, T, G, C
-pairs: AT and GC
What are the four types of nucleotides in mRNA?
A, U, G, C
-pairs: AU and GC
Differentiate transcription and translation.
transcription: gene –> mRNA
translation: mRNA –> protein
How many genes are expressed in a typical human cell?
~15, 000
-expression varies from one cell to another
What is involved in many diseases in regards to genes?
gene malfunction
What are promoters?
DNA sequences that “promote” gene expression
-required for DNA transcription
-direct the exact place to initiate DNA transcription
-determine when and how a gene is transcribed
Where are promoters located?
upstream of genes
-RNA polymerase binding site
What can repress gene transcription?
promoter methylation
What is the Human Genome Project?
discovered complete DNA sequence of human
Differentiate the nuclear DNA genome and the mitochondrial DNA genome.
nuclear:
-22 pairs of autosomes (diploid) and 2 sex chromosomes
- ~ 3 billion base pairs
- ~ 19,000 genes
mitochondrial:
- ~ 17,000 base pairs
- 38 genes
What is ENCODE?
encyclopedia of DNA elements
-annotation of functional elements encoded in human genome
What are gene switches?
non-gene parts of DNA contributing to diseases
-MS, lupus, RA, Crohns
What are the types of genetic variations in the human genome?
single nucleotide polymorphism (SNP)
copy number variations (CNV)
insertions and deletions
large scale variations
structural variations
What is the most common type of genetic variation among people?
SNP
-80% of known polymorphisms
What is an SNP?
small stretches of DNA that differ in only one base
-serve to distinguish individual genetic material
-important in understanding the genetic basis of human disease
-relationship with drug response
How many SNPs are within each gene?
~ 5 coding SNPs
What is the effect of an SNP on each of the following regions of a gene:
-non coding
-regulatory
-coding
non-coding: no effect
regulatory: change expression level
coding: change protein structure–>may change function
What are CNVs?
variation among people in the number of copies for a particular gene or DNA sequence
-source of genetic diversity
-recombination based and replication based mechanisms
What is the predominant mechanism for genome evolution?
gene duplication and exon shuffling
What are some CNVs association with diseases?
cancer
autism
lupus
autoimmune disorders
stroke
What are insertions and deletions?
insertion or deletion of small pieces of DNA
-alternative form of natural genetic variation
What are the five categories of INDELs?
insertion or deletion of single base pairs
expansions by only one base pair
multi-base pair expansions (2-15 repeats)
transposon insertions (inserting mobile elements)
random DNA sequence insertions or deletions
What are large scale variations?
large portions of DNA repeated or missing for no known reasons in healthy persons
-may underlie disease susceptibility
What are structural variations?
kilobase to megabase-sized deletions, duplications, insertions, inversions, and complex combinations of rearrangements
-genome structural changes are involved
What are hot spots?
regions with a lot of variation and often associated with genetic disorders and diseases
-ex: short arm of chromosome 1
What are the types of structural variations?
deletion
duplication
paracentric inversion
balanced translocation
unbalanced translocation
What is molecular diagnosis?
detect specific DNA sequences that may or may not be associated with diseases
Which studies are involved in the “omics”?
genomics
transcriptomics
proteomics
metabolomics
What is genomics?
mapping, sequencing and functional analysis of the genome
Is genomics the same as genetics?
no, they are different
-genetics: look at a single gene
-genomics: look at all genes as an entire system
Differentiate genetics vs genomics.
genetics
-study of heredity
-specific gene
-function and composition of a single gene
genomics
-study of entirety
-entire genome
-address all genes and their relationships
What is transcriptomics?
study of transcriptomes an their functions
What is a transcriptome?
complete set of RNA transcripts produced by the genome
What are the technologies used in transcriptomics?
RNA-Seq and microarray
Differentiate between an exon and an intron.
exon: a portion of a gene that encodes amino acids
intron: a portion of a gene that does not encode amino acids
What is proteomics?
study of proteomes and their functions
What is a proteome?
entire proteins expressed in a cell, tissue or organism
What are the technologies used in proteomics?
2D SDS-PAGE
liquid chromatography
mass spectroscopy
What is metabolomics?
study of metabolites within cells, tissues or organisms
-less or non-invasive and closely linked to phenotype of diseases
What are metabolites?
proteins
lipids
sugars
nucleotides
What are some applications of metabolomics?
biomarker identification
drug safety screens
What is glycomics?
identify the structure and function of the complete set of glycans produced in a given cell or organism and identify all the genes that encode glycoproteins
What is lipidomics?
study of pathways and networks of cellular lipids in biological systems
What are the technologies utilized in lipidomics?
LC
HPLC
NMR
MALDI-MS
What is bioinformatics?
computational approaches to analyze, manage and store biological data
-meeting point for computer science and molecular biology
-analytical method for the “omics”
What are biomarkers?
a biological molecule found in the blood, other body fluids, or tissues that is a sign of a normal or abnormal process, or of a condition or disease
-used to see how well the body responds to a treatment for a disease or condition
What is systems biology and systems medicine?
computational modeling of complex biological systems
biology of interacting networks
facilitate the development of personalized medicine
apply the systems biology technology to medicine
What is the systems approach?
P4 medicine
-predictive
-preventative
-personalized
-participatory
What is conventional medicine?
empirical therapies and mechanism-based therapies
-developed as universal drugs for a certain disease
-diseases with multiple therapies: up to physician experience and preference
What is conventional medicine associated with?
lack of efficacy and adverse effects
What is evidence-based medicine?
highest level of evidence from multiple RCTs
-address a particular clinical problem
evidence-based guidelines may not be suitable for personalized medicine
