Aspek Genetik Gangguan Fungsi luhur dan Keswa

Kiagus M Arsyad Bagian Biologi Kedokteran Fakultas Kendokteran Unsri

TUJUAN PEMBELAJARAN
Agar mahasiswa mengetahui dan memahami tentang : 1. Faktor genetik yang terkait dengan fungsi luhur dan kesehatan jiwa 2. Kaitan faktor genetik dengan otak untuk fungsi luhur dan kesehatan jiwa

MATERI PEMBELAJARAN
1. Pendahuluan 2. Faktor Genetik pada fungsi luhur 3. Faktor Genetik pada Kesehatan Jiwa 4. Penutup

1.PENDAHULUAN
1. 2. 3. 4. 5. Sehat dan sakit Faktor Genetik Fungsi Luhur Kesehatan Jiwa Otak

1.PENDAHULUAN
KESEHATAN Healthy = sound and whole in mind and body, being without physical pain or disease.

Health : The normal physical state, i.e. the state of being whole and free from physical and mental disease or pain, so that all parts of body carry on their proper function,
(Butterworths Medical Dictionary)

1. PENDAHULUAN
DEFINISI SEHAT
WHO (1950) : Health is a state of complete physical, mental and social well being and not merely the absence of disease or infirmity. Indonesia (UU Kes Nas No.23/1992 : Kesehatan adalah keadaan sejahtera dari badan, jiwa, dan sosial yang memungkinkan setiap orang hidup produktif baik secara sosial dan ekonomi.

TIGA FAKTOR PENENTU SEHAT

JASMANI

SEHAT

SOSIAL

MENTAL/ ROHANI

1. PENDAHULUAN
GANGGUAN BIOLOGIS PENYAKIT

GANGGUAN PSIKOLOGIS

SAKIT
GANGGUAN SOSIAL MODEL UNTUK MENJELASKAN TERJADINYA SAKIT (ENGEL 1977)

FAKTOR2 YG BERKORELASI MEMPENGARUHI KESEHATAN

Genotype

Environment

Phenotype

1. PENDAHULUAN
PHENOTYPE GENE GENOTYPE
Ciri Fisik Fungsi Luhur Keswa

ENVIRONTMENT

1. PENDAHULUAN
While showing an impressive growth prenatally, the human brain is not completed at birth. There is considerable brain growth during childhood with dynamic changes taking place in the human brain throughout life, probably for adaptation to our environments.

1. PENDAHULUAN :

2. FAKTOR GENETIKA
Mempelajari pewarisan sifat Genetika = Keeping the faith Gene > genome >> prediktif Khromosom = Seks Khromosom+ autosom

2. FAKTOR GENETIKA
A genetic disorder is a condition caused by abnormalities in genes or chromosomes. the term "genetic disease" most commonly refers to diseases present in all cells of the body and present since conception.

2. FAKTOR GENETIKA
3 macam penyakit genetik : 1. Inherited genetic disease 2. Somatic genetic 3. Chromosomal disorders

2. FAKTOR GENETIKA

Khromosom dan DNA

2. FAKTOR GENETIKA

P=G+E
P = Phenotype E = Environment G = Genotype

2.1.DEFINISI GENOTYPE
GENOTYPE: konstitusi genetik individu, bisa pada semua loci atau yang khas, locus tunggal

2.1. GENOTYPE
genotype dari makhluk instruksi yang diturunkan yang dibawa dengan kode genetiknya. Tidak semua makhluk yang sama genotype kelihatan atau berkerja dengan cara yang sama, karena penampilan dan perilaku dimodifikasi oleh lingkungan dan kondisi perkembangan.

Sebaliknya tidak semua makhluk memiliki genotype yang sama.

2.2. DEFINISI PHENOTYPE

PHENOTYPE : ekspresi genotype yang dapat diamati baik sebagai ciri/ trait atau penyakit,
Phenotype = a trait exhibited by an allele that

distinguishes one individual from another (round vs. wrinkled)

A phenotype is the physical trait or feature of an organism that is the effect of a particular genotype. Ada homozygot dan Heterozygot

2.2. VARIASI PHENOTYPE

Variasi Phenotype (akibat adanya variasi genetik herediter) merupakan persyaratan dasar untuk terjadinya evolusi secara alamiah. Natural selection mempengaruhi struktur genetik populasi secara tidak langsung via kontribusi phenotype. Tanpa adanya variasi phenotype, tidak mungkin adanya evolusi secara natural selection.

2. FAKTOR GENETIKA
ENVIRONMENT :
1. INTERNAL 2. EXTERNAL

GENE

MUTATION

POLYMORPHISM

ABNORMAL PHENOTYPE

DEFINISI

Perubahan Susunan Nukleotida DNA

JENIS

Mutasi Titik Delesi Insersi

t.a.a Fungsi Fungsi Tak berfungsi (inactivated) Sel benih Peny. Keturunan Sel Somatik Kanker DNA Mitokondria (menimbulkan penyakit yang diwariskan garis keturunan ibu)

AKIBAT

LOKASI

Gene phenotypic effect

Regulatory genes Cell-cell interactions

Hormones, gene-product interactions

DNA (Gene)

RNA

Protein

Effect on cell

Effect on tissue

Effect on organism

Environmental effects CENTRAL DOGMA

Effect on organism Effect on organism

2. FAKTOR GENETIKA
Protein

ONE GENE

ONE ENZYME

ONE MANIFESTATION

POLYGENE

POLY ENZYME

POLY MANIFESTATION

POLYMORPHISME

3. FUNGSI LUHUR DAN KESWA

fungsi kehidupan manusia dikendalikan oleh OTAK.

Otak bagaikan pusat pemerintahan yang mengendalikan seluruh wilayah yang menjadi otoritasnya.
Mulai dari menangani informasi yang masuk lewat panca indera, memahaminya, menganalisa, membuat keputusan, sampai pada merespon lewat gerakan anggota tubuh, semua itu diperintah lewat mekanisme otak.

Bahkan, rasa senang, sedih, gembira, mencintai, dan berbagai perasaan kemanusiaan, semua juga berada dan bersumber di otak manusia

3. FUNGSI LUHUR DAN KESWA

Pertanyaannya, kalau begitu apakah Jiwa kita berada di otak itu? Atau bahkan, jangan-jangan, ya otak itu yang disebut Jiwa? kerusakan sel-sel otak bisa menyebabkan Jiwa seseorang terganggu bahkan mengalami kegilaan.

dengan memahami mekanisme kerja OTAK akan dapatt dipahami tentang fungsi otak terhadap fungsi luhur dan kesehatan jiwa

3. FUNGSI LUHUR DAN KESWA

2. OTAK, GAMBAR 1

3. FUNGSI LUHUR DAN KESWA

Genetic continuum of similarity in brain structure. Differences in the quantity of gray matter at each region of cortex were computed for identical and fraternal twins, averaged and compared with the average differences that would be found between pairs of randomly selected, unrelated individuals (blue, left). Color-coded maps show the percentage reduction in intra-pair variance for each cortical region. Fraternal twins exhibit only 30% of the normal inter-subject differences (red, middle), and these affinities are largely restricted to perisylvian language and spatial association cortices. Genetically identical twins display only 1030% of normal differences (red and pink) in a large anatomical band spanning frontal (F), sensorimotor (S/M) and Wernickes (W) language cortices, suggesting strong genetic control of brain structure in these regions, but not others (blue; the significance of these effects is shown on the same color/scale

3. FUNGSI LUHUR DAN KESWA

3. FUNGSI LUHUR DAN KESWA

Correlation between twins in gray matter distribution. Genetically identical twins are almost perfectly correlated in their gray matter distribution, with nearidentity in frontal (F), sensorimotor (S/M) and perisylvian language cortices. Fraternal twins are significantly less alike in frontal cortices, but are 90100% correlated for gray matter in perisylvian language-related cortex,including supramarginal and angular territories and Wernickes language area (W). The significance of these increased similarities, visualized in color, is related to the local intra-class correlation coefficents (r).

3. FUNGSI LUHUR DAN KESWA

3. FUNGSI LUHUR DAN KESWA

3. FUNGSI LUHUR DAN KESWA

Significance of genetic control of gray matter distribution. Brain regions for which cortical gray matter distribution is under significant genetic control are shown in red. Frontal (F) and lateral temporal (T) regions show significant heritability, consistent with their near-identity in identical twins (GB 2) and the weaker patterns of correlations observed in fraternal twins, who have less similar genotypes. Wernickes area shows significantly higher heritability in the left hemisphere (Wleft), which is generally hemisphere (Wleft), which is generally dominant for language function (p < 0.05 for asymmetry).

3. FUNGSI LUHUR DAN KESWA

Human cognition, behavior, and psychiatric disorders involve complex and polygenic modes of inheritance in which each gene might have only a small effect. To date,only the effects of single genetic polymorphisms on brain function have been explored with neuroimaging techniques. Whereas the effects of the COMTval158met polymorphism and the APOE e4 allele on brain function have been consistently shown across many studies, the effects of 5HTT and BDNF polymorphisms, although well supported by evidence from experimental in vitro studies, need replication in independent samples.

3. FUNGSI LUHUR DAN KESWA

The effects of MAO A and DRD4 genotypes are less clear and warrant further study. Most importantly, the functional interactions between multiple gene variants and environment, and their collective impact on brain function are yet to be explored. Overall, the results of some of the studies reviewed in this Article are striking, and they illustrate the promise of brain imaging techniques to unravel the role of genetic polymorphisms in altering brain function as well as in conferring susceptibility to illness. They also underscore the advantage of a systems level approach; that is, integrating genetic information with an endophenotype (i.e. regional neurophysiological, neurochemical and neuroanatomical measures obtained through neuroimaging techniques) and a phenotypic trait (e.g. cognitive and behavioral measures) to successfully delineate the influence of genes on brain function.

3. FUNGSI LUHUR DAN KESWA

Therefore it is difficult to use psychiatric diagnosis as the sole phenotype when studying the genetics of complex (non-Mendelian) disorders, which involve contributions from both genetic and environmental influences and their interactions. Thus, it is difficult to find the genes associated with common complex disorders (e.g. psychiatric disorders) that may result from small effects of many genes (polygenic), incomplete or low penetrance, clinical and genetic heterogeneity, the presence of phenocopies (non-genetic causes), and diagnosis uncertainty.

3. FUNGSI LUHUR DAN KESWA

To the extent that most psychiatric disorders involve a variety of brain dysfunctions, the use of brain oscillations may provide the most informative phenotypes or endophenotypes (intermediate phenotypes). Brain oscillations provide a rich source of potentially useful endophenotypes for psychiatric genetics as they represent important correlates of human information processing and cognition. These quantitative biological markers (endophenotypes) serve as covariates that correlate with the main trait of interest (psychiatric diagnosis) and serve to better define that trait or its underlying genetic mechanism

6. PENUTUP
Faktor genetik pada gangguan fungsi luhur dan kesehatan jiwa dapat berperan sebagai faktor yang diturunkan atau akibat pengaruh lngkungan internal dan eksternal yang mempengaruhi gene dan selanjutnya fenotype Faktor genetik dapat berupa monogenenik , polygenik dan endogenik dengan manifestasi yang beragam (polymorphism)

TUGAS TULIS
Gangguan Fungsi Luhur : 1. Penyakit Alzeimer 2. Autism Gangguan Kesehatan jiwa : 1. Schizophrenia 2. Psikoneurosis 3. psikosis

DAFTAR RUJUKAN
1. Kendler,K.S. Psychiatric Genetic : A metodologic critique, Am.J. Psychiatry,162.1,2005. 2. Thompson,P.,et al., Genetic influences on brain structure,Nature neuroscience, vol.4, no 12 december 2001. 3. Breigleiter,H,Porjesz,B,Genetic on Human Brain oscillaton,Int.J.,Psychophysiology,162:171,2006 4. Cari sendiri