1. Fundamentals Of Human Genome Flashcards
Five common misconceptions about genetics
- Genetics deals with only rare disorder -many are common, diabetes
- Children should not be tested for genetic disorders - only true for adult onset conditions
- Insurance does not pay for genetic testing - yes
- Genetic testing leads to discrimination - GINA prevent discrimination
- Genetic disorders are not treatable - many are
Human genome
2 branches - nuclear genome and mitochondrial genome
Mitochondrial genome: small but highly efficient less than 5% is junk (rRNA, tRNA, protein-coding genes)
Nuclear genome - 80% junk coding DNA (code for proteins 1.25% of genome) non-coding DNA (do not code for protein, regulatory non coding RNA, regulatory functions)
Nucleic Acids
Provide genetic material of cells and viruses
Genes
DNA segments that carry the genetic information to make proteins or functional RNA molecules within the cells
23,000-25,000 protein encoding enzymes in human genome = code for 100,000 proteins
Genome
Collective term for all different DNA molecules within a cell or organism
Distributed between nucleus and mitochondria
Transcriptome
Total set of transcripts in an organism
Expressions of genes modified by external influences (ex: phosphyloration)
Proteome
Protein variation and function expressed by a genome, cell, tissue or organism
Metabolome
Complete set of small-molecule metabolites
such as metabolic intermediates, hormones and other signaling molecules
Human microbiome
Refers to constellation of viruses, bacteria, and fungi that colonize various human tissues
Deoxyribose vs ribose
Deoxyribose in DNA - H on second carbon
Ribose in RNA - OH on second carbon
Purines
Double ring
Adenine (A)
Guanine (G)
Prymadine
Single ring
Thymine (T) - DNA more stable because of methyl group
Uracil (U) - RNA more reactive because of H group
Cytosine (C)
Nucleic acids
Consist of sugar, nitrogenous base and phosphate group
A-T (2 H bonds)
C-G (3 H bonds, stronger)
RNA single nucleotide chain
Chargers rule number of G=C, number to A=T
DNA replication (semi-conservative)
2 stands of double helix are unwound and each strand is used to make a new complementary DNA copy - occurs in S phase of cell cycle
DNA polymerase II — attach new DNA nucleotides
Transcription
Genes are used to make single stranded RNA copy that is complementary in sequence to one of the DNA strands
Produces an RNA copy of gene -mRNA contains information to make a polypeptide
Translation
Coding sequence of mRNA are used to make the polypeptide chain of protein
Polypeptide becomes part of functional protein that contributes to an organisms traits
DNA replication cycle
Transcription - produces RNA copy of gene
MessengerRNA -
Translation - produces polypeptide using the information in the mRNA
Polypeptide -becomes part of functional protein that contributes to an organisms traits
Exons and introns
Our protein coding genes often contain a rather small amount of coding DNA
Coding genes are split into segments called exons that are separated by non coding DNA sequences called introns
RNA splicing
Involves cleaving the RNA transcript at the junctions between transcribed exons and introns
The transcribed exons sequences are then covalently linked (spliced) in turn to make a mature RNA
Complexity comes from using different combinations of exons make alternative transcripts from the same gene - alternative splicing
Synthesized polypeptide to mature protein
Chemical modification
Folding
Cleavage and transport
Binding of multiple polypeptide chains
Sickle cell disease
Most common inherited blood disorder
Point mutation in B-globin - Hb crystallize in low O2 - MI, Stroke, Anemia
SCD: glutamate to valine - protection against falciparum malaria
Pathogenesis: chronic hemolysis, microvascular occlusions and tissue damage
When Hb is deoxygenated - crystallization of membrane occurs - calcium comes in then apoptosis
Obstruct blood vessels and more sticky
Affects bloodstream, heart, brain
Clinical features of SCD
SCD - moderately severe hemolytic anemia -reticulocytosis, hyperbilirubinemia and irreversibly sickled disease
Vaso-occlusive crisis - pain crisis
Acute chest syndrome - priapism, stroke, retinopathy/blindness, autospleenectomy
Chronic hypoxia -generalized impairment of growth and development -organ damage affecting spleen, heart, kidneys, and lungs
Altered splenic functions - susceptibility to infections
Hutchinson - Gifford Progeria Syndrome
Rare fatal genetic condition of childhood (diagnosed around 2 yrs old) with striking features resembling premature against
Sporadic autosomal dominant mutation
Abnormal laminate A (progerin) - abnormal nuclear envelope
Cumulative cellular damage -abnormal aging process
Laminate A/C mutations
Emery-Dreifuss MD/Skeletal myopathy
Progressive AV block and atrial arrhythmia
Worst prognosis than DCM without LMNA mutation
Affects DNA replication - Farnesyl - mutation means farnesyl cannot be cut off laminate A and protein piles up in nuclear envelope
Hutchinson - Gifford Progeria Syndrome Clinical features
Distinctive skin and skeletal defects
Progressive arteriosclerosis and associated cardiovascular abnormalities - life threatening complications
Die in teens
