Genetic and Congenital Disorders, Neoplasia, Mechanisms of Infectious Disease

Gene

Sequence of DNA that encodes a functional product

Genome

complete set of genes in an organism

Genetics

study of genes

Transcription

process of DNA to RNA

Translation

Process of RNA to protein

Transcriptome

complete set of mRNA transcripts

Proteome

complete set of proteins (encoded by a genome)

Proteomics

study of the proteome

Our genome is divided into…

chomosomes

chromosomes are…

packages of the continuous linear DNA helix

Out of the 23 pairs of chromosomes, 1 pair is..

Allosomes

Allosomes are…

sex chromosomes

Out of 23 chromosomes, 22 of them are..

autosomes

autosomes are….

chromosomes that don’t involve a person’s sex

Chromatin

DNA and protein complex

Histones are…

the proteins that package DNA

Function of molecules found on histones

Controlling access to DNA for gene expression

Gene expression leads to…

histone modifications

Histone acetylation turns genes….

ON!

What group opens the chromatin for transcription

an acetyl group

Histone methylation turns genes….

OFF

What group is involved with closing the chromatin

a methyl group

DNA is a template for…

mRNA

mRNA contains..

codons for amino acids

Genes are transcribed by the….

RNA polymerase

Exons are..

a protein coding region in mRNA

Introns are….

non-coding regions in mRNA

Splicing in mRNA is…

editing the regions for mRNA

What happens in splicing

removal of introns and varying segments

Result of Splicing

a variety in protein products

First step of translation

mRNA leaving nucleus and travelling to a ribosome

second step of translation

codons are read by ribosomes, corresponding amino acids are brought by the transfer RNA.

the anticodons on tRNA match with…

mRNA codons

step 3 of translation

Amino acids join together using peptide bonds to create protein

protein synthesis step 1 + result

transcription (DNA to RNA)

protein synthesis step 2 + result

splicing, mRNA

protein synthesis step 3 + result

export, still mRNA

protein synthesis step 4 + result

translation, a.a. chain

protein synthesis step 5 + result

folding, protein

induction

something that turns a gene on

repression

something that turned a gene off

Transcription factors

proteins that initiate and regulate transcription

Epigenetics

Changes in gene expression caused by mechanisms other than changes in DNA sequence

RNA based mechanisms

DNA Methylation

Histone post-translocational modifications

Mutations

Changes in genetic material, but do not always cause a problem

Genotype refers to

someone’s genetic material

Phenotype refers to..

someone’s physical characteristics

Expressivity

how a gene is expressed (mild - severe)

Penetrance

ability of a gene to express its function

Homozygous is when

all genes are alike

Heterozygous is when..

the genes differ

Dominant genes are expressed

if both homozygous or heterozygous

Recessive genes are expressed

only if homozygous for recessive gene

Single gene

One gene drives the trait

Polygenic

Many genes could affect one trait

Multifactorial

Multiple genes and environment could affect trait

Epistasis

when a gene could mask the effect of another

complementary

when one gene might depend on another

Collaborative

when 2 genes together can make a new phenotype

Multiple alleles

if more than 2 alleles affect the same trait

Pedigree

chart that indicates the inheritance of a trait or health condition \n through generations of a family

Autosomal dominant disorders

Marfan syndrome, Huntington’s disease

Autosomal recessive disorders

PKU, Tay-Sachs, sickle cell, cystic fibrosis

X linked recessive disorders

Hemophilia A

Marfan syndrome cause

Gene mutation of extracellular matrix protein abundant in connective tissue (fibrillin – elastic fibers)

Marfan syndrome manifestations

Skeletal abnormalities (long arms, fingers, hyperflexible joints), Vision problems, Cardiovasc complications

Neurofibromatosis cause

Genetic defect in tumor suppressor gene that regulates cell differentiation and growth

How many types of Neurofibromatosis are there

Two

Types of Neurofibromatosis

NF-1: von Recklinghausen disease, and NF-2: bilateral acoustic

von Recklinghausen disease manifestations

neurofibromas in peripheral nerves

Neurofibromatosis manifestations

Tumors developing in the nervous system, Cafe au lait spots

Bilateral acoustic manifestations

Schwann cell tumors, Tumors of acoustic nerve, headache (HA), hearing loss, tinnitus

Phenylketonuria (PKU)

\
Metabolic disorder due to elevated phenylalanine, which is toxic to the brain

Phenylketonuria (PKU) cause

Deficiency in liver enzyme, converts phenylalanine to tyrosine. Aspartame also contains phenylalanine. Catabolism, increasing phenylalanine

Tay-sachs

Lysosomal storage disorder due to lack of hydrolytic enzyme leading to increased sphingolipids in nervous tissue (especially brain). Leads to the destruction of neurons and gradual deterioration of motor \n and mental function. No treatment: fatal at 4-5 years of age

Bio females sex phenotype

XX

Bio males sex phenotype

XY

For X linked recessive disorders, if mom is carrier…

Daughters: 50% chance of carrier

Sons: 50% chance of having disease + affected male will give X gene to all daughters

X linked dominant disorders

where theres a mutant x, which becomes dominant to normal x

True or false: both biologic sexes are affected by x linked dominant disorders

true

true or false : Affected females (heterozygous – X\*X) transmit the mutant X chromosome to 50% of offspring regardless of sex

true

Would affected biologic males have affected daughters and normal sons? Given other parent doesn’t have mutated X chromosomes

Yes

Chromosomal disorders types

Structural Chromosomal Abnormalities, Numeric Autosomal

Structural Chromosomal Abnormalities

Break in chromosome followed by rearrangement or deletion of parts

Numeric autosomal

Change in chromosome number of autosome

Numeric autosomal examples

Down Syndrome – Trisomy 21, XXY (Klinefelter Syndrome) – 47 chromosomes, 45 X,0 (Turner Syndrome) – 45 chromosomes

most common chromosomal disorder

Trisomy 21 / down syndrome

Down syndrome manifestations

Intellectual disability, Physical characteristics, Congenital heart defects, Increased risk of Acute lymphoblastic leukemia and GI malformations.

Turner Syndrome cause

Absence of all (45, X0) or part of X chromosome

Turner syndrome manifestations

May vary depending on chromosomal abnormalities \n • Mosaicism - multiple cell lines \n • Short stature \n • Ovarian dysgenesis \n • May have cardiac abnormalities

Turner syndrome treatment

Treatment with growth hormone and estrogen therapy

Mitochondrial DNA disorders

Inherited primarily from the parent who provided the egg – can be traced back through generations

a neoplasm is…

a tumor

Neoplasm

an abnormal mass of tissue in which growth exceeds and is uncoordinated with that of normal tissues

Two modes of Neoplasm

Benign or malignant

Benign neoplasms

Not threatening. Usually encapsulated and slows down / stops growth. does not pass go, doesn’t metastasize

Anaplasia

Loss of mature or specialized features of a cell or tissue

how do cancer cells differ from normal cells

differentiation is low, they do not need a growth factor hormone, growth is very unregulated