DNA to Protein

• Human body is mad up of numerous cells and each cell

has nucleus containing chromosome and chromosome
contain the genetic material called DNA

• A gene is a sequence of DNA or RNA that codes for a

molecule that has a function (protein)
•CENTRAL DOGMA provides the basic
framework for how genetic information
flows from a DNA sequence to a protein
product inside cells. This process of genetic
information flowing from DNA to RNA to
protein is called gene expression.
• DNA replication is the biological process of producing two identical
replicas of DNA from one original DNA molecule by the enzyme DNA
polymerase
• Transcription is the first step of gene expression, in which a particular
segment of DNA is copied into RNA by the enzyme RNA polymerase
• Translation is the process in which ribosome synthesize proteins in
the cytoplasm after the process of transcription, it has 3 prime steps:
• INITIATION
• ELONGATION
• TERMINATION
DNA Methylation
• DNA Methylation is a process by which methyl groups are
added to the DNA molecule.
• Methylation can change the activity of a DNA segment without
changing the sequence.
• When located in a gene promoter, DNA methylation typically acts to
repress gene transcription.
• DNA methylation acts as an epigenetic modification in vertebrate
DNA. Recently it has become clear that the DNA and histone lysine
methylation systems are highly interrelated and rely mechanistically
on each other for normal chromatin function in vivo.
• Pseudogenes are genomic DNA sequences similar to normal genes
but nonfunctionally are regarded as non existing relatives of
functional genes.
• Pseudogene are abundant in the genome
• Post-transcriptional modification is the process in eukaryotic cells
where primary transcript RNA is converted into mature RNA
• A notable example is the conversion of precursor mRNA into mature
mRNA that occurs prior to protein translation.
• The process includes three major steps:
• Addition of a 5' cap
• Addition of a 3' poly-Adenylation tail
• Splicing
Human Genetics and Genome
Analysis
Basic Terms
• Gene: A hereditary unit consisting of a sequence of DNA that
occupies a specific location on a chromosome and determines a
particular characteristic in an organism.
• Trait: A distinguishing feature, a genetically determined characteristic
or condition.
• Allele: Versions of a gene
• Genotype: Genetic makeup, distinguished from the physical
appearance. (G for genetic and genotype)
• Phenotype: The observable physical or biochemical characteristics as
determined by both genetic makeup and environment
Basic Terms
• Classical Dominance: Dominant allele is expressed if present
• Incomplete Penetrance: Not all individuals with a mutant genotype
display the phenotype (many genetics Diseases but good example is
NF1)
• Variable Expression: Nature and severity of phenotype changes
between individuals
• Co-dominance: Neither of two alleles is dominant (e.g. blood types)
• Anticipation: Severity of disease worsens or age of onset is earlier in
succeeding generations (e.g. Huntington’s Disease)
Basic Terms
• Loss of heterozygosity: When a tumor suppressor gene is mutated or
deleted, the complimentary allele must be lost before a cancer
develops. Not true with oncogenes!
• Dominant negative mutation: a non-functioning protein also
prevents a normal protein from functioning appropriately
• Heteroplasmy: Both Normal and mutant mtDNA results in variable
expression in mitochondrial inherited Diseases
• Uniparental disomy: offspring receives 2 copies of a chromosome
from 1 parent and none from the other
Pedigree Analysis
Modes of Inheritance
Autosomal Dominant: • Examples:
• Achondroplasia, Huntington’s
• Affects both males and Disease, Neurofibromatosis
females in all types 1 & 2
generations.
• Presents clinically after
puberty and final hight is
essential for diagnosis.
Huntington’s Disease
Modes of Inheritance
Autosomal Recessive: • Examples:
• Albinism
• only offspring of 2 carrier parents • Cystic Fibrosis
can be affected.
• Usually only seen in one
generation, usually due to
enzyme deficiencies.
• Commonly more severe than
dominant disorders, presents in
childhood
Modes of Inheritance
X-Linked Recessive • Examples:
• Hemophilia A and B
• Only sons of heterozygous
mothers can be affected, no
father to son transmission.
• Females may rarely be
affected due to random
inactivation of X chrom (e.g.
Lyonization)
Modes of Inheritance
X-linked dominant • Example:
• Hypophosphatemic rickets
•Transmitted through increased phosphate wasting at
proximal tubule
both parents, males
and females can be
affected, but all
females of affected
fathers are affected.
Human X-Linked Traits
Modes of Inheritance
Mitochondrial
• Transmission ONLY
through the mother.
• All offspring of affected
mothers are affected.
• Variable expression due to
heteroplasmy