ASPEK GENETIK

PADA GANGGUAN
FUNGSI LUHUR DAN
KESEHATAN JIWA

Dr. Mitayani, M.Si. Med.

 Neural differentiation is a default state that
manifests unless it is inhibited.
 Gen

mRNA Protein
 Transcription factors participate in decisions
of determining the generic neural cells such
as neuron or glial cells.
TRANSKRIPSI
 Faktor transkripsi akan berikatan dengan
sekuens DNA spesifik yang disebut promoter
sequences (TATA box).
 Ikatan ini akan mengundang RNA polimerase
untuk menempel pada titik awal transkripsi.
 Faktor transkripsi + RNA polymerase =
kompleks inisiasi transkripsi.
ALZHEIMER
 Associated with microglial cells.
 Gene for Amyloid precursor proteins is
located in chr 21q.
ALZHEIMER
PARKINSON
 SNCA = synuclein, α (non A4 component of
amyloid precursor)
 SNCA is the major constituent of Lewy
bodies, the neuropathological hallmark of
Parkinson Disease, and mutations and gene
dosage variations in SNCA cause Parkinson
Disease.
SCHIZOPHRENIA
 Schizophrenia is a multifactorial disease.
 What is multifactorial disease?

Risk factors:
 Prenatal and birth complications
 Family history
 Body dysmorphia
SCHIZOPHRENIA
 Structural abnormalities: smaller prefrontal
cortex and hippocampus; enlarged
ventricles.
 Apa peranan genetik dalam timbulnya
keabnormalan tersebut?
SCHIZOPHRENIA
 Smaller hippocampus may result from subtle
differences in the level of transcription
factors such as NeuroD, Math1, Lhx.
 This genetic limitation may only become
manifest following another developmental
challenge such as gestational infection,
stressors, or toxicant exposure.
SCHIZOPHRENIA
 Increased rate among the biological relatives
of patients with schizophrenia.
 Modes of inheritance is still unknown.
SCHIZOPHRENIA
 One of candidate genes is DISC1.
 Its protein has roles: regulating cell
migration, neurite outgrowth, and neuronal
maturation.
 Other linkage sites: chromosomes 1q, 5q, 6p,
6q, 8p, 10p, 13q, 15q.
SCHIZOPHRENIA
AUTISM SPECTRUM DISORDER
Candidate gene:
 ENGRAILED-2: causes deficits in Purkinje and
granule neurons in animal models and acts to
control proliferation and differentiation.
 cMET: affects migration of GABA
interneurons, leading to imbalances of
excitatory and inhibitory neurotransmissions.
TERIMA KASIH