PSYC20008 Lecture 12: Lecture 12 - Human Genetics (2)
14 Jun 2018
School
Department
Course
Professor
PSYC20006 - DEVELOPMENTAL PSYCHOLOGY
LECTURE 12
HUMAN GENETICS (2)
THIS LECTURE:
•Genetic transmission of disorders
•Phenotype and Genotype
•Epigenetics
GENETIC ORIGINS OF DISEASE
•Over 5,000 human diseases and disorders are presently known to have genetic origins.
•Different types of genetic disorders.
•Recessive gene: PKU, sickle-cell anemia, Tay- Sachs disease, cystic fibrosis.
•Need 2 copies of the gene to show the phenotype. If 1 copy, can pass on to children.
•Single dominant gene: Huntington’s disease, neurofibromatosis.
•Only need 1 copy of gene to show phenotype.
•Polygenic inheritance: cancer, heart disease, asthma, psychiatric disorders, behavior disorders.
•Poly = many. Many genes contribute to these disorders.
•Sex-Linked inheritance: red-green color blindness, hemophilia, Duchenne muscular dystrophy,
fragile-X syndrome.
•Chromosomal anomalies: Down syndrome (trisomy 21), Kleinfelter syndrome (XXY), Turner
syndrome (XO).
•Regulator gene defects: genetic male with female genitalia.
•Unidentified (poorly understood) genetic basis: autism spectrum disorder (ASD), Attention Deficit
Hyperactivity Disorder (ADHD) (most likely polygenic).
TAY-SACHS DISEASE
•Tay Sachs disease is a fatal, autosomal recessive neurodegenerative disease of infancy and early
childhood. It is rare in most populations and is caused by mutations of HEXA gene on
chromosome 15q23-q24.
•Autosomal = not on sex chromosomes.
•It was first identified in 1969. One of the earliest genetic disorders to be identified.
•Population studies and pedigree analyses suggest that mutations may have arisen from small
founder populations: small founder populations = a new world disorder = someone from the old
world (Africa, Asia) has migrated to a part of the new world carrying mutation while carrying the
mutation.
•Carrier frequency is 1:25 in Ashkenazi Jews.
•Same mutation is found in Cajun population in southern Louisiana.
•Two different mutations are common in French Canadians (people moving from France to
Canada a few centuries ago).
•Higher carrier frequency in Irish-American and Pennsylvania Dutch communities compared
with general population.
•Incidence in unscreened Jewish populations is 1 in 3,900 births.
•Internationally, screening has reduced the incidence of Ashkenazi Jews with TSD-affected
children by more than 90%.
•To avoid passing on tay Sachs to offspring, we can use IVF screening (to see if embryo is carrying
2 copies of a gene)
•Australian high-school-based preconception genetic screening programs help young people
through screening and education.
•Aim is to optimise reproductive choices for participants.
•Plans to extend the program into the more general Ashkenazi Jewish community.
PSYC20006 - DEVELOPMENTAL PSYCHOLOGY
HUNTINGTON’S DISEASE
•Autosomal dominant = not on sex chromosomes, only need 1 copy of the gene to show
phenotype.
•Huntingtin gene isolated in 1993, on chromosome 4 at 4p16.3.
•40 repeats of CAG (cytosine, adenine, guanine) trinucleotide in coding region of gene is what
causes it.
•Huntington’s disease is an insertion mutation.
•Mean onset ~40 yrs, death 12-15 yrs afterwards.
•Prevalence 5-10 per 100,000. Relatively rare.
•Symptoms include cognitive deterioration, personality change, memory loss and depression, and
choreic and slow movement.
•Used to be called Huntington’s Chorea. Affects basal ganglia and frontal cortex; areas for
movement control.
•Therapeutic research:
•Mechanisms of neuronal death
•Cell replacement therapy
CHOREA AND BRADYKINESIA CHARACTERISE SLOW MOVEMENT IN HUNTINGTON’S
BROADER SUB CORTICAL AND CORTICAL DAMAGE IN HUNTINGTON’S COMPARED
WITH PARKINSON’S DISEASE
•Neuronal and astrocyte loss in the basal ganglia (caudate, putamen, global pallidus and other
areas).
•Selective degeneration of GABAergic neurons of striatum.
•As disease progresses, greater cortical atrophy occurs.
•The gene contains an expanded trinucleotide repeat (CAG) that ranges from 9-35 in healthy
adults, and from 36 !
to 180 in HD.
•Alleles with 36-39 repeats show reduced
penetrance - only some individuals will go
on to develop clinical symptoms.
•Individuals with juvenile onset (Westphal
variant) usually have expansions >55
repeats and develop HD before 20 years.
•Onset appears to be earlier when the
transmission is from the father.
