Unit 2 Pathphysiology - Chapter 6 Epigenetics and Disease Flashcards
3 major epigenetic processes
Overview of Epigenetic Mechanisms
- DNA methylation: attachment of a methyl group to a cytosine; in somatic cells, all or nearly all methylation occurs at cytosines binded with guanines
When gene heavily methylated, DNA less likely to transcribe into mRNA - HIstone modification: methylation and acetylation most studied
HIstones => bind to DNA, modify chromatin shape and regulate activity of genes
Histone acetylation remove positve charge of histones => reduce their binding strength to negatively charged DNA => more DNA accessible for transcription (Acetylating the histone reduces how tightly DNA is wrapped around the nucleosome, thus allowing transcription machinery to more easily enter)
BONUS — HIstone methylation can either strengthen or weaken bonding between DNA and histones
- noncoding RNAs (ncRNAs or miRNAs or microRNAs): from introns of protein coding genes or transcribed as independent genes from regions of genome with unknown functions; microRNAs regulate diverse signaling pathways
When twins age, what happens to their phenotypes?
Overview of Epigenetic Mechanisms
Due to aging, there are differences in methylation patterns of DNA l/t increased # of phenotypic differences.
Transcriptionally active versus inactive (gene silencing)
Genomic Imprinting
A given gene (either from father or mother it is designated) is only transcriptionally active on one copy of a chromosome; on other copy (determined by other precondition whether it be father or mother) is transcriptionally inactive
depends on who transmit gene will determine which gene will be silnced; the silenced gene is “imprinted”
What is different about an imprinted allele
Genomic Imprinting
dense w/ DNA methylation; nonimprinted allele is not methylated
Humans inherit two alleles from mother and father, both are functional for the majority of the genes, but sometimes one is turned off or “stamped” and doesn’t show in offspring, that gene is imprinted. Imprinting means that that gene is silenced, and gene from other parent is expressed.
Prader-Willi syndrome
Genomic Imprinting
deletion of approximately 4 million Mb or base pairs of long arm (chromosome 15); when father inherits it then child will manifest it
- early infancy: hypotonia, poor appetite, feeding difficulties
- early childhood: excessive eating and gradual morbid obesity (unless controlled intake)
- motor milestones and language devlopment - delayed
Angelman syndrome
Genomic Imprinting
same 4-Mb deletion as prader-willi syndrome when inherited by mother
- delayed development
- intellectual disability
- severe speech impairment
- ataxia (impaired mvmt and balance)
Beckwith-Wiedemann syndrome
Genomic Imprinting
overgrowth condition (r/t imprinting) accompanied by an increased predisposition to cancer // upregulation of active IGF2 (growth factor 2) causes this overgrowth
- large body size @ birth, large tongue, hypoglycemia
- taller than avg height during childhood
Russell-silver syndrome
intrauterine growth restriction; downregulation of IGF2 causes diminished growth
- poor growth after birth
- large head, traingle facial appearance, prominent forehead
- body assymmetry
- significant feeding difficulties
Alcohol during pregnancy
Epigenetics in Cognitive Development and Mental Health
Fetal alcohol syndrome (cognitive abnormalities) via altered methylation of genes invovled in neuronal differentiation
- FAS ^^^^^^
- low body weight, poor coordination, hyperactive
- poor attention, memory
- learning disability
- speech + lang delay
Do people with autism, PTSD have altered DNA methylation profiles?
Epigenetics in Cognitive Development and Mental Health
yes
Fragile X syndrome
Epigenetics in Cognitive Development and Mental Health
interaction (genetic & epigenetic abnormalities) + a lot of methylation
- cognitive impairment, learning disabilities
- delayed milestones, gestures + body language as well
- math and language delay
- male more severely affected; usually by age 2
Facioscapulohumeral muscular dystrophy (FSHD)
caused by abnormal loss of methylation
- teen years (noticible in infancy)
- muscle weakness and wasting (atrophy)
- face, shoulder blades, and upper arms
- less recognized - hamstring and trunk + other limbs
- slow progression
- autosomal dominant genetic condition
Can identical twins diverge epigenetically
Epigenetic Change over the Life Span
Yes through enviornmental factors such as tobacco use
What can metformin do?
Epigenetic Change over the Life Span
Prolong life through epigenetic mechanisms
Bisulfite conversion
Epigenetic Change over the Life Span
makes changes to cytosine and methylcytosine in terms of binding properties, to be distingushed in sequence data
