ÁÍÁÓÊÏÐÇÓÇ

ÁÑ×ÅÉÁ ÅËËÇÍÉÊÇÓ ÉÁÔÑÉÊÇÓ 2001, 18(5):475–484

REVIEW ARCHIVES OF HELLENIC MEDICINE 2001, 18(5):475–484

E. ÊáíáâÜêçò,
Ç ÷áñôïãñÜöçóç ôïõ áíèñþðéíïõ ãïíéäéþìáôïò Á. ÎáúäÜñá

Ç ÷áñôïãñÜöçóç ôïõ áíèñþðéíïõ ãïíéäéþìáôïò, ôï ìåãáëýôåñï ìÝ÷ñé óÞìåñá

ÅñãáóôÞñéï ÉáôñéêÞò ÃåíåôéêÞò,
åã÷åßñçìá óôçí éóôïñßá ôçò âéïëïãßáò, Üëëáîå ñéæéêÜ ôçí éáôñéêÞ ðñÜîç. Ôï áí-
ÐáíåðéóôÞìéï Áèçíþí,
èñþðéíï ãïíéäßùìá ðåñéÝ÷åé ôï óýíïëï ôçò ãåíåôéêÞò ðëçñïöïñßáò êáé áðïôå- Íïóïêïìåßï Ðáßäùí «Áãßá Óïößá», ÁèÞíá
ëåßôáé áðü 3 ðåñßðïõ äéóåêáôïììýñéá âÜóåéò, ðïõ êáôáíÝìïíôáé óôá 22 áõôï-
óùìáôéêÜ ÷ñùìïóþìáôá êáé ôá 2 ÷ñùìïóþìáôá ôïõ öýëïõ. Õðïëïãßæåôáé üôé
õðÜñ÷ïõí 50.000–100.000 ãïíßäéá, ôùí ïðïßùí ïé êùäéêïðïéïýóåò ðåñéï÷Ýò êá-
The human genome project
ëýðôïõí ðåñßðïõ 2–3% ôïõ óõíïëéêïý DNA, ôïõ ðñùôáñ÷éêïý ìïñßïõ ôçò æùÞò.
Ôï áíèñþðéíï ãïíéäßùìá åßíáé ÷áñáêôçñéóôéêü ôïõ áíèñþðéíïõ åßäïõò, äåí åß- Abstract at the end of the article
íáé áðüëõôá üìïéï, áëëÜ óå ðïëëïýò ãåíåôéêïýò ôüðïõò åìöáíßæïíôáé 2 Þ 3
áëëçëüìïñöá, ïé ðïëõìïñöéóìïß. Ç ÷áñôïãñÜöçóç ôïõ áíèñþðéíïõ ãïíéäéþ-
ìáôïò Üñ÷éóå ôï 1990 áðü ôçí áêáäçìáúêÞ êïéíüôçôá, óôçí ïðïßá ðñïóôÝèçêå
êáé ç éäéùôéêÞ ðñùôïâïõëßá ôï 1998. Ïé äýï ïìÜäåò áíáêïßíùóáí ôáõôü÷ñïíá ËÝîåéò åõñåôçñßïõ
ôá áðïôåëÝóìáôÜ ôïõò (26-6-2000 êáé 15-2-2001). Ôá ìÝ÷ñé óÞìåñá êáé ôá á- Áíèñþðéíï ãïíéäßùìá
íáìåíüìåíá ïöÝëç áöïñïýí ôç ãåíåôéêÞ äéÜãíùóç êáé ôéò íÝåò èåñáðåõôéêÝò ÃåíåôéêÞ
ìåèüäïõò. Ç ãåíåôéêÞ äéÜãíùóç åöáñìüæåôáé ãéá ôçí ðñüëçøç (ðñïãåííçôéêÞ- Ãïíßäéá
ðñïåìöõôåõôéêÞ äéÜãíùóç) êáé ôçí ðñïêëéíéêÞ äéÜãíùóç ìïíïãïíéäéáêþí íï- DNA ÷áñôïãñÜöçóç
óçìÜôùí. Ðåñßðïõ 1.000 ãåíåôéêÜ íïóÞìáôá Ý÷ïõí ìåëåôçèåß óå ìïñéáêü åðß- Ðïëõìïñöéóìïß
ðåäï êáé Ý÷åé áðïìïíùèåß ôï õðåýèõíï ãéá ôï íüóçìá ãïíßäéï êáé ïé áíôßóôïé-
÷åò ìåôáëëÜîåéò. ¼óïí áöïñÜ ôá ðïëõãïíéäéáêÜ íïóÞìáôá, ç áíß÷íåõóç ôçò
ãåíåôéêÞò ðñïäéÜèåóçò óå óõíäõáóìü ìå ôçí áðïöõãÞ óõãêåêñéìÝíùí ðåñé-
âáëëïíôéêþí åðéäñÜóåùí èá ïäçãÞóåé óôç ìåßùóç ôïõ êéíäýíïõ åêäÞëùóçò
ôïõ íïóÞìáôïò Þ óôçí áíáóôïëÞ ôçò åðéäåßíùóçò ôçò êëéíéêÞò ôïõ ðïñåßáò. Ç
èåñáðåõôéêÞ ðñïóðÝëáóç ôùí íïóçìÜôùí áíáìÝíåôáé íá âåëôéùèåß ìå ôï ó÷å-
äéáóìü êáé ôçí ðáñáãùãÞ öáñìÜêùí êáôÜëëçëùí ãéá ôï ãåíåôéêü õðüóôñùìá
ôïõ áóèåíïýò, Ýôóé þóôå íá áõîçèåß ç áðïôåëåóìáôéêüôçôá êáé íá ðåñéïñé-
óôïýí ïé áíåðéèýìçôåò åíÝñãåéåò ôùí öáñìÜêùí. ÅðéðëÝïí, ç ãïíéäéáêÞ èåñá-
ðåßá èá åîáóöáëßóåé ñéæéêÞ áíôéìåôþðéóç ôùí ãåíåôéêþí íïóçìÜôùí êáé ôá íïõ-
êëåúêÜ ïîÝá, ìå ôñüðï äñÜóçò áíÜëïãï ìå áõôüí ôùí ìïíïêëùíéêþí áíôéóù-
ìÜôùí, èá ÷ñçóéìïðïéçèïýí óå ðïëëÜ íïóÞìáôá. ÏõóéáóôéêÞ âïÞèåéá óôçí ï-
ëïêëÞñùóç ôçò ÷áñôïãñÜöçóçò ôïõ áíèñþðéíïõ ãïíéäéþìáôïò ðñïóöÝñåé ç
óõãêñéôéêÞ ãïíéäéùìáôéêÞ, ç ðáñÜëëçëç äçëáäÞ ÷áñôïãñÜöçóç ôïõ ãïíéäéþ-
ìáôïò ðñüôõðùí ïñãáíéóìþí, ç ïðïßá ðáñÝ÷åé ðëçñïöïñßåò ãéá ôçí áíáæÞôç-
óç ãïíéäßùí õðåýèõíùí ãéá ðïëõãïíéäéáêÜ êõñßùò íïóÞìáôá êáé ãéá ôï Üìåóï
«ðåñéâÜëëïí» ôùí ãïíéäßùí. Ïé çèéêÝò, íïìéêÝò êáé êïéíùíéêÝò åðéðôþóåéò ôçò
÷áñôïãñÜöçóçò ôïõ áíèñþðéíïõ ãïíéäéþìáôïò ìåëåôþíôáé (ðñüãñáììá ELSI-
Ethical, Legal, Social Implications), ìå óêïðü íá èåóðéóôåß ç áíÜëïãç íïìïèå-
óßá êáé íá äéáìïñöùèïýí êþäéêåò êïéíùíéêÞò óõìðåñéöïñÜò, ðïõ èá äéáóöá-
ëßæïõí ôï áðüññçôï, ôçí áôïìéêüôçôá êáé ôçí éäéïêôçóßá ôçò ãåíåôéêÞò ðëçñï-
öïñßáò êáé èá ðñïóôáôåýïõí ôá áíèñþðéíá äéêáéþìáôá.

1. ÅÉÓÁÃÙÃÇ ç ìåôáìüó÷åõóç ïñãÜíùí êáé ìõåëïý ôùí ïóôþí, ïé ï-

Óôç äéÜñêåéá ôïõ 20ïý áéþíá, ç éáôñéêÞ åðéóôÞìç åõ-
ôý÷çóå íá äåé ìéá óåéñÜ áðü åðáíáóôáôéêÝò áíáêáëý-
øåéò, ðïõ áðïôÝëåóáí ôç âÜóç ãéá ôçí áíÜðôõîç äéá-
ãíùóôéêþí êáé èåñáðåõôéêþí ðáñåìâÜóåùí, üðùò ôá á-
íôéâéïôéêÜ, ôá åìâüëéá, ïé íÝåò áðåéêïíéóôéêÝò ìÝèïäïé,
ðïßåò Üëëáîáí ñéæéêÜ ôç æùÞ ôùí áíèñþðùí óôéò áíá-
ðôõãìÝíåò ÷þñåò.
Ïé áëëáãÝò áõôÝò, ðïõ Ý÷ïõí Þäç áñ÷ßóåé íá ãßíïíôáé
åìöáíåßò, áíáìÝíïíôáé ñáãäáßåò ìåôÜ ôçí ïëïêëÞñùóç
ôçò ÷áñôïãñÜöçóçò ôïõ áíèñþðéíïõ ãïíéäéþìáôïò, ðïõ
476
ðñïÝêõøå áðü ôç óõíôïíéóìÝíç åñåõíçôéêÞ ðñïóðÜèåéá
ôçò áêáäçìáúêÞò êïéíüôçôáò êáé ôçò éäéùôéêÞò ðñùôï-
âïõëßáò.
Âáóéêü óôü÷ï ôïõ ìåãÜëïõ áõôïý äéåèíïýò åã÷åéñÞ-
ìáôïò áðïôÝëåóå ç áðüêôçóç áñ÷éêÜ âáóéêþí ðëçñï-
öïñéþí ðïõ áöïñïýí ôï ãåíåôéêü ìáò õðüóôñùìá êáé ç
áíÜëõóç êáé óýíèåóç ôùí ðëçñïöïñéþí áõôþí ãéá ðëç-
ñÝóôåñç êáôáíüçóç ôïõ ñüëïõ ôùí äéáöüñùí ãïíéäßùí
óôç äéáôÞñçóç ôçò õãåßáò êáé ôç äçìéïõñãßá ôçò íüóïõ.
2. ÂÁÓÉÊÇ ÌÏÑÉÁÊÇ ÂÉÏËÏÃÉÁ
Ôï áíèñþðéíï ãïíéäßùìá ðåñéÝ÷åé ôï óýíïëï ôçò ãå-
íåôéêÞò ðëçñïöïñßáò êáé áðïôåëåßôáé áðü 3 ðåñßðïõ äé-
óåêáôïììýñéá âÜóåéò êáôáíåìçìÝíåò óôá 22 áõôïóù-
ìáôéêÜ ÷ñùìïóþìáôá êáé ôá 2 ÷ñùìïóþìáôá ôïõ öý-
ëïõ.1–3
Ôï ãåíåôéêü õëéêü ðïõ êëçñïíïìåßôáé áðü ôïõò ãïíåßò
åßíáé áõôü ðïõ êáèïñßæåé ü÷é ìüíï ôá åîùôåñéêÜ ÷áñá-
êôçñéóôéêÜ ôïõ áôüìïõ, áëëÜ åðßóçò ôç ìïñéáêÞ âÜóç
ôçò ïñãáíïãÝíåóçò, ôçò ïìïéüóôáóçò êáé ôçò áíáðáñá-
ãùãÞò. ÅðéðëÝïí, ç âÜóç üëùí ôùí ãåíåôéêþí áíùìá-
ëéþí âñßóêåôáé óå áëëáãÝò ðïõ åðéóõìâáßíïõí óôï ìü-
ñéï ôïõ DNA.
Ôï DNA (äåóïîõñéâïíïõêëåúêü ïîý) åßíáé, óõíåðþò,
ôï ðñùôáñ÷éêü ìüñéï ôçò æùÞò êáé áðïôåëåßôáé áðü äýï
äéáöïñåôéêÝò ïìÜäåò áæùôïý÷ùí âÜóåùí, ôéò ðïõñßíåò
(áäåíßíç, ãïõáíßíç, Á, G) êáé ôéò ðõñéìéäßíåò (èõìßíç,
êõôïóßíç, Ô, C).
Ôï 1953, ïé Watson êáé Crick áðïêÜëõøáí ôç äåõôå-
ñïôáãÞ äïìÞ ôïõ ìïñßïõ ôïõ DNA, ôï ïðïßï áðïôåëåß-
ôáé áðü ìéá äéðëÞ Ýëéêá. Ï êÜèå êëþíïò ôçò Ýëéêáò á-
ðïôåëåßôáé áðü Ýíá ðïëõìåñÝò óáê÷Üñïõ-öùóöïñéêþí
ïìÜäùí, üðïõ ôï óÜê÷áñï (äåóïîõñéâüæç) êáé ïé öù-
óöïñéêÝò ïìÜäåò åíþíïíôáé ìå åóôåñéêïýò äåóìïýò.
Óôç èÝóç 1 ôïõ óáê÷áñéêïý äáêôõëßïõ âñßóêåôáé êÜ-
ðïéá áðü ôéò ôÝóóåñéò áæùôïý÷åò âÜóåéò (Á, Ô, G, C). Ç
Ýëéêá óõãêñáôåßôáé ìå äåóìïýò õäñïãüíïõ, ðïõ áíá-
ðôýóóïíôáé ìåôáîý ôùí óõìðëçñùìáôéêþí âÜóåùí. Ãéá
ëüãïõò ðïõ ïöåßëïíôáé êáèáñÜ óôç ÷çìéêÞ óýóôáóç ôùí
âÜóåùí, ç ãïõáíßíç «æåõãáñþíåé» ìüíï ìå ôçí êõôïóß-
íç ìå ôç âïÞèåéá ôñéþí õäñïãïíéêþí äåóìþí êáé ç á-
äåíßíç ìüíï ìå ôç èõìßíç ìå ôç âïÞèåéá äýï õäñïãï-
íéêþí äåóìþí. Ó÷çìáôßæïíôáé Ýôóé äýï ðïëõíïõêëåïôé-
äéêÝò áëõóßäåò, ðïõ ðåñéåëßóóïíôáé äåîéüóôñïöá ç ìéá
ãýñù áðü ôçí Üëëç.1–4
Áí ôï DNA áðü Ýíá ìïíáäéêü êýôôáñï îåäéðëùèåß å-
íôåëþò, ôüôå èá åêôáèåß óå ìÞêïò 2 m. ÐñÝðåé, óõíå-
ðþò, íá õðÜñ÷åé êÜðïéá ìÝèïäïò «ðáêåôáñßóìáôïò» é-
äéáßôåñá áðïôåëåóìáôéêÞ. Ãéá ôï ëüãï áõôü, óôá êýôôá-
Å. ÊÁÍÁÂÁÊÇÓ êáé Á. ÎÁÚÄÁÑÁ
ñá ôùí èçëáóôéêþí ëåéôïõñãåß Ýíá ðïëýðëïêï óýóôçìá
ðåñéÝëéîçò, ôï ïðïßï öáßíåôáé íá óõììåôÝ÷åé êáé óôïí Ý-
ëåã÷ï ôçò ãïíéäéáêÞò Ýêöñáóçò.
Óôï áíèñþðéíï ãïíéäßùìá õðïëïãßæåôáé üôé õðÜñ÷ïõí
50.000–100.000 ãïíßäéá, ôùí ïðïßùí ïé êùäéêïðïéïý-
óåò ðåñéï÷Ýò êáëýðôïõí ðåñßðïõ 2–3% ôïõ óõíïëéêïý
DNA. Ôï ìéêñüôåñï áðü áõôÜ ôá ãïíßäéá ìðïñåß íá êá-
ôáëáìâÜíåé ëéãüôåñï áðü ìåñéêÝò åêáôïíôÜäåò, åíþ ôï
ìåãáëýôåñï ðåñéóóüôåñï áðü Ýíá åêáôïììýñéï æåýãç âÜ-
óåùí. Ôï ìç ìåôáãñáöüìåíï DNA oíïìÜæåôáé «äéáãï-
íéäéáêü» DNA êáé öáßíåôáé íá óõììåôÝ÷åé óôçí áíôé-
ãñáöÞ ôïõ DNA êáé óôçí Ýêöñáóç üëùí ôùí ñõèìéóôé-
êþí ãïíéäßùí.
Ôï áíèñþðéíï ãïíéäßùìá, ðáñüôé åßíáé ÷áñáêôçñéóôé-
êü ôïõ áíèñþðéíïõ åßäïõò, äåí åßíáé áðüëõôá ßäéï, ðá-
ñÜ ìüíï óôïõò ìïíïùïãåíåßò äéäýìïõò. ¸ôóé, åßíáé ðï-
ëý óõ÷íü, ãéá ðïëëïýò ãåíåôéêïýò ôüðïõò íá åìöáíß-
æïíôáé 2 Þ 3 öõóéïëïãéêÜ áëëçëüìïñöá óå Ýíáí ðëç-
èõóìü. Ïé äéáöïñåôéêïß áõôïß ãïíüôõðïé, ðïõ áêïëïõ-
èïýí ôïí áðëü ìåíôÝëåéï ôñüðï êëçñïíïìéêüôçôáò, ÷á-
ñáêôçñßæïíôáé ùò ðïëõìïñöéóìïß ôïõ DNA. Ôï öáéíü-
ìåíï ôïõ ðïëõìïñöéóìïý åßíáé ðïëý åêôåôáìÝíï êáé óå
áõôü ïöåßëåôáé ç ãåíåôéêÞ ðïéêéëüôçôá êáé ç ìïíáäéêü-
ôçôá ôùí áôüìùí. Ôá óõ÷íüôåñá åßäç ìéêñïäéáöïñï-
ðïéÞóåùí óôçí áëëçëïõ÷ßá ôïõ DNA ìåôáîý ôùí áôü-
ìùí åßíáé:1,2,5–11
á. ÌéêñïäïñõöïñéêÝò áëëçëïõ÷ßåò. Åßíáé åðáíáëáìâá-
íüìåíåò áëëçëïõ÷ßåò äé-, ôñé- Þ ôåôñá-íïõêëåïôéäßùí
óôï ãïíéäßùìá. ÕðÜñ÷ïõí ìåãÜëåò äéáöïñïðïéÞóåéò
áðü Üôïìï óå Üôïìï, ðïõ áöïñïýí ôï ìÝãåèïò êáé
ôïí áñéèìü ôïõò. Áðïôåëïýí ÷ñÞóéìá åñãáëåßá ãéá ïé-
êïãåíåéáêÝò ìåëÝôåò, Ýëåã÷ï ðáôñüôçôáò êáé óôçí Éá-
ôñïäéêáóôéêÞ.
â. ÌéíéäïñõöïñéêÝò áëëçëïõ÷ßåò. Áðïôåëïýí åðáíá-
ëáìâáíüìåíá ôìÞìáôá DNA ìåãÝèïõò 1 kb Þ ìåãá-
ëýôåñá, ôïðïèåôçìÝíá Ýôóé, þóôå óôï ôÝëïò ôçò ìßáò
íá áêïëïõèåß ç áñ÷Þ ôçò åðüìåíçò. ÁíáöÝñïíôáé ùò
VNTR áëëçëïõ÷ßåò (variable number of tandem re-
peats).
ã. ÄéáöïñÝò åíüò íïõêëåïôéäßïõ (SNP) (single nucleo-
tide polymorphism). Áðïôåëïýí ôïõò óõ÷íüôåñïõò ôý-
ðïõò äéáöïñïðïéÞóåùí. Õðïëïãßæåôáé üôé õðÜñ÷åé 1
SNP óå êÜèå 1.000 ðåñßðïõ âÜóåéò. Áðïôåëïýí é-
ó÷õñü üðëï, óÞìåñá, ãéá ôç äéÜãíùóç êáé ôç ìåëÝôç
ãåíåôéêþí íïóçìÜôùí, éäéáßôåñá ðïëõãïíéäéáêþí, êá-
èþò êáé ãéá ôç öáñìáêïãåíåôéêÞ.
Ïé ðïëõìïñöéóìïß áõôïß ìðïñïýí åðßóçò íá ÷ñçóé-
ìïðïéçèïýí ãéá ðñïãåííçôéêÞ êáé ðñïêëéíéêÞ äéÜãíù-
óç êáé áíß÷íåõóç öïñÝùí, åöüóïí ôï õðåýèõíï ãïíß-
äéï ãéá ôï ãåíåôéêü íüóçìá äåí åßíáé ãíùóôü. ×ñçóé-
ÁÍÈÑÙÐÉÍÏ ÃÏÍÉÄÉÙÌÁ 477

ìïðïéïýíôáé åðßóçò ãéá ìåëÝôåò óýíäåóçò êáé áíß÷íåõ- Ðßíáêáò 1. Óôáäéïðïßçóç ôïõ ðñïãñÜììáôïò ÷áñôïãñÜöçóçò ôïõ áí-
óç áôüìùí ðïõ âñßóêïíôáé óå êßíäõíï ãéá ãåíåôéêü íü- èñþðéíïõ ãïíéäéþìáôïò.
óçìá. Óôü÷ïò ×ñïíéêÞ ðåñßïäïò
ÊÜèå êëçñïíïìïýìåíç áëëáãÞ óôçí áëëçëïõ÷ßá ôïõ 1993–2003
DNA ïíïìÜæåôáé ìåôáëëáãÞ. ÐïëëÝò áðü ôéò ìåôáëëá- Ãåíåôéêüò ÷Üñôçò Ïëïêëçñþèçêå
ãÝò åðéäéïñèþíïíôáé, ÷ñçóéìïðïéþíôáò ôç ìç êáôå-
Öõóéêüò ÷Üñôçò Ïëïêëçñþèçêå
óôñáììÝíç áëõóßäá ôïõ DNA ùò ìÞôñá ãéá ôçí åðé-
äéüñèùóç ôçò Üëëçò. Áí üìùò ç êáôáóôñïöÞ áöïñÜ êáé DNA sequencing ÓçìåñéíÞ êáôÜóôáóç (26/6/00)
ôéò äýï áëõóßäåò Þ áí áõôÞ óõìâåß ëßãï ðñéí Þ êáôÜ ôï ÁíÜðôõîç ôå÷íïëïãßáò áõôüìáôïõ
äéðëáóéáóìü, ôüôå ç âëÜâç ðáñáìÝíåé óôïõò áðïãüíïõò sequencing êáé ôå÷íïëïãßáò
ôïõ êõôôÜñïõ.1,2 ðëçñïöïñéêÞò ÐñïïäåõôéêÞ âåëôßùóç

Ç óõ÷íüôçôá ôùí ìåôáëëáãþí áíÝñ÷åôáé óôï 1/1.000.000 ÌåëÝôç ôçò åôåñïãÝíåéáò »200.000–300.000 SNPs
ðåñßðïõ âÜóåùí DNA. ÅÜí ëÜâïõìå õðüøç üôé õðÜñ- óôï áíèñþðéíï ãïíéäßùìá áõôïìáôïðïéçìÝíç áíß÷íåõóç
(ðïëõìïñöéóìïß SNPs) (óõíå÷ßæåôáé)
÷ïõí ðåñßðïõ 50.000–100.000 ãïíßäéá, áõôü óçìáßíåé
üôé 5–10% ôùí íåïãÝííçôùí öÝñïõí ìéá íÝá ìåôáëëá- Åíôüðéóç ãïíéäßùí Óõíå÷ßæåôáé
ãÞ. Ïé ðåñéóóüôåñåò áðü áõôÝò åßíáé åõôõ÷þò óéùðçëÝò, ÌåëÝôç Ýêöñáóçò ãïíéäßùí Óõíå÷ßæåôáé
åðåéäÞ ôï áíôßóôïé÷ï ãïíßäéï óôï ïìüëïãï ÷ñùìüóùìá ÁíÜëõóç ãïíéäéþìáôïò
åßíáé öõóéïëïãéêü êáé åîéóïññïðåß ôç âëÜâç. Üëëùí ïñãáíéóìþí
(óõãêñéôéêÞ ãïíéäéùìáôéêÞ)
3. ÉÓÔÏÑÉÊÇ ÁÍÁÄÑÏÌÇ ÔÇÓ ×ÁÑÔÏÃÑÁÖÇÓÇÓ – Çaemophilus influenzae (1830 kb) Oëïêëçñþèçêå (1995)
– Ìycoplasma genitalium (580 kb) Ïëïêëçñþèçêå (1995)
ÔÏÕ ÁÍÈÑÙÐÉÍÏÕ ÃÏÍÉÄÉÙÌÁÔÏÓ
– Å. coli (5.000 kb) Ïëïêëçñþèçêå
Ïé áñ÷éêÝò óêÝøåéò ãéá ôï üëï åã÷åßñçìá ôÝèçêáí ôï – Drosophila (160.000 kb) Óõíå÷ßæåôáé (»2002)
– Ðïíôßêé Óõíå÷ßæåôáé (»2005)
1984, êáôÜ ôç äéÜñêåéá åíüò óõíåäñßïõ, ìå óêïðü ôçí
áíß÷íåõóç ôùí ìåôáëëÜîåùí óå Üôïìá ðïõ åß÷áí åðé-
âéþóåé áðü ôçí åðßäñáóç ôçò áôïìéêÞò âüìâáò. ÔÝóóå-
ñá ÷ñüíéá áñãüôåñá (1988), óôï ÍÉÇ (National Institute – ÌåëÝôç Ýêöñáóçò ãïíéäßùí
of Health) éäñýèçêå õðçñåóßá ãéá ôçí Ýñåõíá óôï áí-
– ÁíÜëõóç ãïíéäéþìáôïò Üëëùí ïñãáíéóìþí (óõãêñéôé-
èñþðéíï ãïíéäßùìá ìå õðåýèõíï ôïí James Watson, ç
êÞ ãïíéäéùìáôéêÞ).
ïðïßá óôï ôÝëïò ôïõ ßäéïõ ÷ñüíïõ áíáâáèìßóôçêå êáé
ìåôáôñÜðçêå óå åèíéêü êÝíôñï. Äýï ÷ñüíéá áñãüôåñá, Ôï ÷ñïíïäéÜãñáììá ôïõ ðñïãñÜììáôïò áíáôñÜðçêå
ôçí 1/10/1990, Üñ÷éóå åðßóçìá ç Ýíáñîç ôçò ÷áñôï- ñéæéêÜ ìåôÜ ôçí áíÜìéîç ôçò éäéùôéêÞò ðñùôïâïõëßáò óôï
ãñÜöçóçò ôïõ áíèñþðéíïõ ãïíéäéþìáôïò. Ðïëý óýíôï- üëï åã÷åßñçìá, ôï 1998.
ìá, ôï ðñüãñáììá Ýãéíå äéåèíÝò ìå ôç óõììåôï÷Þ êáé
Ç åôáéñßá Celera Genomics, äéÜ ôïõ åêðñïóþðïõ ôçò
Üëëùí, åêôüò ôùí ÇÐÁ, ÷ùñþí, üðùò ç Áããëßá, ç Ãáë-
Graig Venter, áíÝëáâå íá ïëïêëçñþóåé ôç ÷áñôïãñÜ-
ëßá, ç Éôáëßá, ç Ãåñìáíßá, ï ÊáíáäÜò êáé ç Éáðùíßá. Ï
öçóç ôïõ ãïíéäéþìáôïò óå 3 ÷ñüíéá, ìåéþíïíôáò êáôÜ
óõíôïíéóìüò ðáñÝìåéíå óôéò ÇÐÁ êáé ãßíåôáé áðü ðï-
4 ïëüêëçñá ÷ñüíéá ôï ÷ñïíéêü äéÜóôçìá ðïõ åß÷å êá-
ëõðëçèÞ åðéóôçìïíéêÞ ïìÜäá, ôçò ïðïßáò óÞìåñá çãåßôáé
èïñßóåé ç äéåèíÞò ïìÜäá ôïõ äçìüóéïõ öïñÝá, ç ïðïßá
ï Francis Collins.12–14
óôá ðëáßóéá ôïõ áíôáãùíéóìïý åíôáôéêïðïßçóå ôéò ðñï-
O áñ÷éêüò ðñïãñáììáôéóìüò, ï ïðïßïò Þôáí 15åôÞò, êáé óðÜèåéÝò ôçò.
ç óôáäéïðïßçóç ôïõ ðñïãñÜììáôïò, üðùò äéáìïñöþèçêå
×ñçóéìïðïéþíôáò äéáöïñåôéêÞ ìåèïäïëïãßá, ïé äýï
ìåôÜ áðü ðïëëÝò ôñïðïðïéÞóåéò, Ý÷åé ùò åîÞò (ðßí. 1):
ïìÜäåò Ýêáíáí ôáõôü÷ñïíá ôçí ðñþôç áíáêïßíùóç ôùí
– Êáèïñéóìüò ôïõ ãåíåôéêïý êáé öõóéêïý ÷Üñôç áðïôåëåóìÜôùí ôïõò óå êïéíÞ åìöÜíéóç óôéò 26 Éïõíß-
– ÁíÜëõóç ôçò áëëçëïõ÷ßáò ôïõ DNA ïõ 2000.

– ÁíÜðôõîç ôå÷íïëïãßáò áõôüìáôçò áíÜëõóçò ôçò áë- Ç ïìÜäá ôïõ äçìüóéïõ öïñÝá áíáêïßíùóå üôé Ý÷åé
ëçëïõ÷ßáò ôïõ DNA êëùíïðïéÞóåé ôï 97% ôïõ ãïíéäéþìáôïò êáé Ý÷åé ðñï-
÷ùñÞóåé óôçí áíÜëõóç ôçò áëëçëïõ÷ßáò ôïõ óå ðïóïóôü
– ÌåëÝôç åôåñïãÝíåéáò óôï áíèñþðéíï ãïíéäßùìá-ðï- 85% åðôÜ öïñÝò. Áðü ôï ôìÞìá áõôü, ìüíï ôï 24% Þ-
ëõìïñöéóìïß SNPs ôáí ðëÞñùò ïëïêëçñùìÝíï ìå áíÜëõóç õøçëÞò áêñß-
– Åíôüðéóç ãïíéäßùí âåéáò, ôï 22% Þôáí ó÷åäüí Ýôïéìï êáé ôï 38% âñéóêü-
478
ôáí óå ðñü÷åéñç ìïñöÞ. Óôï õðüëïéðï ôìÞìá ç äéáäé-
êáóßáò ôçò áíÜëõóçò óõíå÷ßæåôáé, åêôüò áðü Ýíá 3%, ôïõ
ïðïßïõ ç áíÜëõóç ðáñïõóéÜæåôáé éäéáßôåñá äýóêïëç.
Ç ïìÜäá ôïõ éäéùôéêïý öïñÝá áíáêïßíùóå ôç ÷áñôï-
ãñÜöçóç ôïõ 99% ôïõ ãïíéäéþìáôïò, ÷ùñßò üìùò íá õ-
ðåéóÝñ÷åôáé óå ðåñéóóüôåñåò ëåðôïìÝñåéåò.15–21
Ôçí áíáêïßíùóç áõôÞ, ðïõ ðñïóäéïñßæåé ôï ôÝëïò ìéáò
óõíáñðáóôéêÞò êáé éóôïñéêÞò óçìáóßáò áðïóôïëÞò êáé
åðéôåýãìáôïò êáé ðïõ áðïôåëåß ôï ìåãáëýôåñï óôáèìü
ôçò óýã÷ñïíçò âéïëïãßáò, áêïëïýèçóáí áñêåôÝò óõæç-
ôÞóåéò ìåôáîý ôùí ìåëþí ôçò åðéóôçìïíéêÞò êïéíüôçôáò.
ÁõôÝò Ý÷ïõí ùò óêïðü ôçí øý÷ñáéìç áîéïëüãçóç ôùí
áðïôåëåóìÜôùí êáé ôïí êáèïñéóìü ôùí åðüìåíùí óôü-
÷ùí ãéá óùóôÞ åêìåôÜëëåõóç ôçò íÝáò ãíþóçò, óôï-
÷åýïíôáò óôç âåëôßùóç êáé ôñïðïðïßçóç ôùí äéáãíù-
óôéêþí êáé èåñáðåõôéêþí ðñïóåããßóåùí ôá åðüìåíá
÷ñüíéá.
Ôá ìÝ÷ñé óÞìåñá áëëÜ êáé ôá áíáìåíüìåíá ïöÝëç êáé
ïé åðåñ÷üìåíåò åðéäñÜóåéò óôï ÷þñï ôùí âéïúáôñéêþí
åðéóôçìþí óõíïøßæïíôáé ùò åîÞò (åéê. 1):
á. Áíß÷íåõóç êáé ìåëÝôç ôùí ãïíéäßùí ðïõ óõíäÝïíôáé
ìå óõãêåêñéìÝíá íïóÞìáôá (ìïíï- êáé ðïëõ-ãïíé-
äéáêÜ)
â. Ðñüëçøç ãåíåôéêþí íïóçìÜôùí
ã. ÄéÜãíùóç ãåíåôéêþí íïóçìÜôùí óå ðñïêëéíéêü å-
ðßðåäï
ä. Êáèïñéóìüò êéíäýíïõ ãéá åìöÜíéóç ãåíåôéêïý íï-
óÞìáôïò
å. Áíß÷íåõóç ðïëõìïñöéêþí óçìåßùí (SNPS) ãéá êá-
èïñéóìü ôçò ãåíåôéêÞò éäéáéôåñüôçôáò ôïõ áôüìïõ
Åéêüíá 1. Áíáìåíüìåíá ïöÝëç áðü ôç ÷áñôïãñÜöçóç ôïõ áíèñþðéíïõ ãïíéäéþìáôïò.
Å. ÊÁÍÁÂÁÊÇÓ êáé Á. ÎÁÚÄÁÑÁ
óô. ÅöáñìïãÞ íÝùí èåñáðåõôéêþí ìåèüäùí (öáñìá-
êïãåíåôéêÞ, ãïíéäéáêÞ èåñáðåßá, íïõêëåúêÜ ïîÝá)
æ. ÌåëÝôç ôùí ðñùôåúíéêþí ðáñáãþãùí ôùí ãïíéäßùí
êáé ôçò áëëçëåðßäñáóÞò ôïõò óå êõôôáñéêü åðßðåäï
(proteomics)
ç. ÌåëÝôç ôçò áëëçëåðßäñáóçò ôùí ãïíéäßùí êáé ôùí
ðñùôåúíþí ãéá ôçí åðßôåõîç óýíèåôùí âéïëïãéêþí
ëåéôïõñãéþí
è. ÁíÜëõóç ôïõ ãïíéäéþìáôïò Üëëùí ïñãáíéóìþí.
Óôéò 15 Öåâñïõáñßïõ 2001 áêïëïýèçóáí ôáõôü÷ñï-
íá äýï íÝåò îå÷ùñéóôÝò äçìïóéåýóåéò áðü 2 ïìÜäåò. Á-
ðü ôéò áíáêïéíþóåéò áõôÝò ðñïêýðôåé üôé ç ÷áñôïãñÜ-
öçóç ôïõ áíèñþðéíïõ ãïíéäéþìáôïò êáëýðôåé ðåñßðïõ
ôï 94% ôïõ óõíïëéêïý ãïíéäéþìáôïò. ÌÝ÷ñé óÞìåñá, ðå-
ñßðïõ 1 äéóåêáôïììýñéï âÜóåéò âñßóêïíôáé óôçí ôåëéêÞ
ôïõò ìïñöÞ êáé áíáìÝíåôáé íá ïëïêëçñùèåß óýíôïìá ï
ðñïóäéïñéóìüò ôùí áëëçëïõ÷éþí ôïõò.22,23
4. ÃÅÍÅÔÉÊÇ ÄÉÁÃÍÙÓÇ-ÐÑÏËÇØÇ,
ÐÑÏÊËÉÍÉÊÇ ÄÉÁÃÍÙÓÇ, ÃÅÍÅÔÉÊÇ ÐÑÏÄÉÁÈÅÓÇ
Ïé ìïñéáêÝò ôå÷íéêÝò ÷ñçóéìïðïéïýíôáé ôçí ôåëåõôáßá äå-
êáåôßá ìå ìåãÜëç åðéôõ÷ßá óôç äéÜãíùóç äéáöüñùí ãåíå-
ôéêþí íïóçìÜôùí. Ç äéÜãíùóç áöïñÜ ôüóï ôçí ðñüëçøç
üóï êáé ôçí ðñïêëéíéêÞ äéÜãíùóç. Óå åðßðåäï ðñüëçøçò,
ïé ôå÷íéêÝò áõôÝò ÷ñçóéìïðïéïýíôáé ãéá áíß÷íåõóç öïñÝ-
ùí êáé ðñïãåííçôéêü Ýëåã÷ï. Ãéá ôá íïóÞìáôá åêåßíá ãéá
ôá ïðïßá äåí õößóôáôáé ìåèïäïëïãßá, áéìáôïëïãéêÞ Þ âéï-
÷çìéêÞ, ãéá ôïí êáèïñéóìü ôùí öïñÝùí, ïé ìïñéáêÝò ôå-
÷íéêÝò åöáñìüæïíôáé ãéá åõñåßá ïéêïãåíåéáêÞ ìåëÝôç óå
ïéêïãÝíåéåò ðïõ Ý÷ïõí Þäç áðïêôÞóåé Üññùóôï ðáéäß.
ÁÍÈÑÙÐÉÍÏ ÃÏÍÉÄÉÙÌÁ 479

Ç ìåèïäïëïãßá áõôÞ åßíáé åðßóçò áðüëõôá áêñéâÞò

êáé áðïôåëåóìáôéêÞ ãéá ôïí ðñïãåííçôéêü Ýëåã÷ï ìï-
íïãïíéäéáêþí íïóçìÜôùí êáé Ý÷åé áñ÷ßóåé íá åöáñìü-
æåôáé óå óõíäõáóìü ìå ôçí åîùóùìáôéêÞ ãïíéìïðïßçóç,
ãéá ðñïåìöõôåõôéêÞ ãåíåôéêÞ äéÜãíùóç, åðéëÝãïíôáò ìü-
íï öõóéïëïãéêÜ Ýìâñõá ãéá åìöýôåõóç óôç ìÞôñá. ÌÝ-
÷ñé óÞìåñá, ðåñßðïõ 1.000 ãåíåôéêÜ íïóÞìáôá Ý÷ïõí
ìåëåôçèåß óå ìïñéáêü åðßðåäï êáé Ý÷åé áðïìïíùèåß ôï
õðåýèõíï ãéá ôç íüóï ãïíßäéï êáé ïé ìåôáëëÜîåéò óôá
ãïíßäéá áõôÜ.2–4,11,24–28
Ç áíß÷íåõóç ôïõ íïóÞìáôïò ðñéí áðü ôçí åêäÞëùóç
êëéíéêÞò óõìðôùìáôïëïãßáò åßíáé áðïäåêôÞ åðéóôçìïíé- Åéêüíá 2. Áëëçëåðßäñáóç ãåíåôéêþí ðáñáãüíôùí êáé ðåñéâÜëëïíôïò
êÜ ãéá ôá íïóÞìáôá åêåßíá óôá ïðïßá ç Ýãêáéñç äéÜ- óôçí åêäÞëùóç ôïõ ãåíåôéêïý íïóÞìáôïò.
ãíùóç êáé èåñáðåõôéêÞ ðáñÝìâáóç ìðïñåß íá ðñïëÜ-
âåé ôçí åîÝëéîç ôïõ íïóÞìáôïò Þ íá âåëôéþóåé ôçí êëé-
íéêÞ ôïõ ðïñåßá. ÕðÜñ÷ïõí, ðáñüëá áõôÜ, áñêåôÝò óõæçôÞóåéò êáé ðñï-
âëçìáôéóìïß ãéá ôçí áîßá ôïõ áíùôÝñù åëÝã÷ïõ, ìå ôï
Áíôßèåôá, Ý÷ïõí õðÜñîåé ðïëëÝò óõæçôÞóåéò ãéá ôç åíäå÷üìåíï ôçò øõ÷ïëïãéêÞò åðéâÜñõíóçò ôùí áôüìùí
÷ñçóéìüôçôá ôçò ðñïêëéíéêÞò äéÜãíùóçò ãéá íïóÞìáôá êáé ôïõ Üã÷ïõò ðïõ óõíïäåýåé ìéá ôÝôïéá ðñüâëåøç. Ïé
ìå êáèõóôåñçìÝíç êëéíéêÞ åêäÞëùóç, üðùò ç íüóïò ôïõ óõæçôÞóåéò áõôÝò áíáìÝíïíôáé íá äéáäñáìáôßóïõí êá-
Huntington. èïñéóôéêü ñüëï ãéá ôç ãåíßêåõóç åíüò ôÝôïéïõ åëÝã÷ïõ
Ìå ôçí ïëïêëÞñùóç ôçò ÷áñôïãñÜöçóçò ôïõ ãïíéäéþ- óôïí ôïìÝá ôçò ðñïëçðôéêÞò ÉáôñéêÞò.40–47
ìáôïò, ï ôïìÝáò ôçò äéÜãíùóçò áíáìÝíåôáé íá áðïêïìß-
óåé ôá ðåñéóóüôåñá ïöÝëç ìå ôç äéåýñõíóç ôïõ öÜóìá- 5. ÈÅÑÁÐÅÉÁ
ôïò ôùí ãåíåôéêþí íïóçìÜôùí óôá ïðïßá èá ìðïñÝóåé íá
ðñïóöåñèåß ç ðñïãåííçôéêÞ äéÜãíùóç, ôçí åðÝêôáóç ôïõ 5.1. ÖáñìáêïãåíåôéêÞ
åëÝã÷ïõ ãéá áíß÷íåõóç öïñÝùí ãåíåôéêþí íïóçìÜôùí óå Ç öáñìáêïãåíåôéêÞ áðïôåëåß Ýíá íÝï êëÜäï ôùí âéï-
ðëçèõóìéáêü åðßðåäï ìå áõôïìáôïðïéçìÝíç ìåèïäïëï- ëïãéêþí åðéóôçìþí, ðïõ óôï÷åýåé óôï ó÷åäéáóìü êáé ôçí
ãßá êáé ôçí áíß÷íåõóç áôüìùí ðïõ âñßóêïíôáé óå õøçëü ðáñáãùãÞ öáñìáêåõôéêþí ðñïúüíôùí ðïõ èá âáóßæï-
êßíäõíï (ãåíåôéêÞ ðñïäéÜèåóç) ãéá ðïëõðáñáãïíôéêÜ íï- íôáé óå óõãêåêñéìÝíï ãåíåôéêü ÷áñáêôçñéóôéêü ôïõ á-
óÞìáôá, üðùò êáñêßíï, óáê÷áñþäç äéáâÞôç, áñôçñéï- óèåíïýò Þ ïìÜäáò áóèåíþí, ìå óêïðü íá ðåñéïñéóôïýí
óêëÞñùóç. Óôéò ðåñéðôþóåéò áõôÝò ï Ýëåã÷ïò åðéâÜëëå- óôï åëÜ÷éóôï ïé áíåðéèýìçôåò åíÝñãåéåò ôïõ öáñìÜêïõ
ôáé, üôáí ç Ýãêáéñç áíôéìåôþðéóç ôïõ íïóÞìáôïò ìðïñåß êáé ôáõôü÷ñïíá íá áõîçèåß ç áðïôåëåóìáôéêüôçôÜ ôïõ
íá áíáóôåßëåé ôçí åðéäåßíùóç ôçò êëéíéêÞò ôïõ ðïñåßáò. óå èåñáðåõôéêü åðßðåäï.3,48–50
ÅðéðëÝïí, ç áðïöõãÞ ïñéóìÝíùí ðåñéâáëëïíôéêþí åðé-
Åßíáé áðüëõôá åîáêñéâùìÝíï óÞìåñá üôé ôüóï ç áðï-
äñÜóåùí èá ìðïñïýóå íá åëáôôþóåé ôïí êßíäõíï åêäÞ-
ôåëåóìáôéêüôçôá üóï êáé ïé áíåðéèýìçôåò åíÝñãåéåò å-
ëùóçò ôùí ðïëõãïíéäéáêþí áõôþí íïóçìÜôùí óå Üôïìá
íüò öáñìÜêïõ åîáñôþíôáé áðü äéÜöïñïõò ãåíåôéêÜ êá-
ôá ïðïßá öÝñïõí ãåíåôéêÝò äéáôáñá÷Ýò ðïõ ðñïäéáèÝôïõí
èïñéóìÝíïõò ðáñÜãïíôåò, üðùò ôçí áðïññüöçóç êáé
ãéá ôçí åêäÞëùóç ôçò íüóïõ (åéê. 2).29–39
êáôáíïìÞ ôïõ óôïõò éóôïýò, ôï ìåôáâïëéóìü ôïõ, ôç óõ-
Åßíáé åðßóçò ãíùóôü üôé ï óõóôçìáôéêüò êáé óå óõ- ãêÝíôñùóÞ ôïõ óôï óçìåßï-óôü÷ï êáé ôïí áñéèìü êáé ôç
ãêåêñéìÝíá ÷ñïíéêÜ äéáóôÞìáôá åñãáóôçñéáêüò Ýëåã÷ïò ìïñöïëïãßá ôùí õðïäï÷Ýùí äñÜóçò ôïõ.
èá ìðïñïýóå íá åíôïðßóåé Ýíá íüóçìá ãåíåôéêÜ åðéâá-
Êëáóéêü ðáñÜäåéãìá ãåíåôéêÜ êáèïñéóìÝíçò áíåðéèý-
ñçìÝíï áðü ôá ðñþôá óôÜäéá ôçò åêäÞëùóÞò ôïõ, ïðü-
ìçôçò åíÝñãåéáò áðïôåëåß ç ðåñéöåñéêÞ íåõñïðÜèåéá ðïõ
ôå êáé áíáìÝíåôáé íá åßíáé áðïôåëåóìáôéêüôåñç ç üðïéá
ó÷åôßæåôáé ìå ôç ÷ñÞóç ôçò éóïíéáæßäçò ãéá ôç èåñáðåßá ôçò
èåñáðåõôéêÞ ðáñÝìâáóç. ÊëáóéêÜ ðáñáäåßãìáôá áðï-
öõìáôßùóçò. Ç íåõñïðÜèåéá áõôÞ åìöáíßæåôáé óå áóèå-
ôåëïýí ç ðïëõðïäßáóç ôïõ åíôÝñïõ êáé ï êáñêßíïò ôïõ
íåßò ðïõ öÝñïõí ôï óõãêåêñéìÝíï ðïëõìïñöéóìü ôïõ ãï-
ìáóôïý.
íéäßïõ ðïõ åêöñÜæåé ôï óõíÝíæõìï Í-áêåôõëïôñáíóöåñÜ-
Ï êáôÜëïãïò ôùí íïóçìÜôùí áõôþí óõíå÷þò áõîÜíåé óç-2 óôï Þðáñ. Ç ðáñïõóßá ôïõ ðïëõìïñöéóìïý áõôïý Ý-
êáé áíáìÝíåôáé íá äéåõñõíèåß ïõóéáóôéêÜ ôá åðüìåíá ÷åé ùò óõíÝðåéá ôç âñáäåßá áêåôõëßùóç ôïõ öáñìÜêïõ
÷ñüíéá, ìåôÜ ôçí ïëïêëÞñùóç ôçò ÷áñôïãñÜöçóçò ôïõ óôï Þðáñ êáé ôçí ðáñáìïíÞ ôïõ óå õøçëÜ åðßðåäá óôçí
áíèñþðéíïõ ãïíéäéþìáôïò. êõêëïöïñßá. Ãéá ôïí êáèïñéóìü ôïõ ãåíåôéêïý ÷áñáêôÞ-
480
ñá ôùí áóèåíþí ÷ñçóéìïðïéïýíôáé áðïôåëåóìáôéêÜ óÞ-
ìåñá ïé ðïëõìïñöéóìïß ìéáò âÜóçò ôïõ DNA (SNPs), ðïõ,
üðùò õðïëïãßæåôáé, áðáíôïýí ìå óõ÷íüôçôá 1/1.000 ðå-
ñßðïõ âÜóåéò. Ãéá ôçí ïëïêëÞñùóç åíüò óõãêåêñéìÝíïõ
ðïëõìïñöéêïý ÷Üñôç (SNPs map) Ý÷åé óõóôáèåß ìéá ìç
êåñäïóêïðéêïý ÷áñáêôÞñá åôáéñåßá óôçí Áããëßá, ðïõ á-
ðïôåëåßôáé áðü öáñìáêåõôéêÝò åôáéñåßåò, åôáéñåßåò ðëçñï-
öïñéêÞò, áêáäçìáúêÜ éíóôéôïýôá êáé ôçí åôáéñåßá Welcome
Foundation. Óêïðüò ôçò åôáéñåßáò áõôÞò åßíáé ç óýíèåóç
åíüò ÷Üñôç áðü 200.000–300.000 ðåñßðïõ SNPs ìÝ÷ñé ôï
2003.4,7–11 Ìå ôç âïÞèåéá ôçò ðëçñïöïñéêÞò õðïëïãßæåôáé
üôé èá êáôáóôåß äõíáôÞ ç óõó÷Ýôéóç ïñéóìÝíùí ðïëõìïñ-
öéóìþí óå êÜèå áóèåíÞ ìå óõãêåêñéìÝíç êÜèå öïñÜ öáñ-
ìáêåõôéêÞ áãùãÞ. Ïé ðëÝïí áéóéüäïîåò ôïðïèåôÞóåéò óôï
èÝìá áõôü ðñïâëÝðïõí üôé ìåëëïíôéêÜ èá åßíáé äõíáôÞ ç
÷ñÞóç Ç/Õ óå êÜèå éáôñåßï ãéá ôï ó÷åäéáóìü ôçò êáôáë-
ëçëüôåñçò èåñáðåõôéêÞò ðñïóÝããéóçò ãéá êÜèå áóèåíÞ
÷ùñéóôÜ. Ìå ôç ÷ñÞóç ôçò öáñìáêïãåíåôéêÞò áíáìÝíåôáé
åðßóçò üôé èá åëáôôùèåß óçìáíôéêÜ ôï êüóôïò ðáñáóêåõ-
Þò åíüò öáñìÜêïõ, êáèþò êáé ï ÷ñüíïò áðü ôçí áíáêÜ-
ëõøÞ ôïõ ìÝ÷ñé ôç äéÜèåóç ãéá ÷ñÞóç áðü ôïõò áóèåíåßò.
5.2. ÃïíéäéáêÞ èåñáðåßá
Ç ãïíéäéáêÞ èåñáðåßá õðüó÷åôáé íá áðïôåëÝóåé ôçí ï-
ñéóôéêÞ ëýóç ãéá ôç èåñáðåõôéêÞ áíôéìåôþðéóç ôùí ìï-
íïãïíéäéáêþí íïóçìÜôùí. ÐáñÜ ôï ãåãïíüò üôé ïé åñåõ-
íçôéêÝò ðñïóðÜèåéåò ðñïò ôçí êáôåýèõíóç áõôÞ óõíå÷ß-
æïíôáé áìåßùôåò ôéò ôåëåõôáßåò 2–3 äåêáåôßåò, õðÜñ÷ïõí
áêüìá ðïëëÜ ðñïâëÞìáôá ðïõ ðåñéïñßæïõí, ðñïò ôï ðá-
ñüí, óôï åëÜ÷éóôï ôéò äõíáôüôçôåò åöáñìïãÞò ôçò óå êëé-
íéêü åðßðåäï. Ôá ðñïâëÞìáôá áõôÜ áöïñïýí êõñßùò ôçí
áíÜðôõîç êáôÜëëçëùí óõóôçìÜôùí ìåôáöïñÜò ðñïò ôá
êýôôáñá-óôü÷ïõò ãéá ôç äéüñèùóç ôçò ãåíåôéêÞò âëÜâçò.
Ïé ðåñéóóüôåñåò åñåõíçôéêÝò ðñïóðÜèåéåò åóôéÜæïíôáé
óôç äéüñèùóç ôçò ãåíåôéêÞò âëÜâçò óôá óùìáôéêÜ êýô-
ôáñá, åíþ õðÜñ÷ïõí ðïëëÝò áíôéññÞóåéò ãéá áíÜëïãåò
ðáñåìâÜóåéò óôá ãåííçôéêÜ êýôôáñá. Óôçí ðåñßðôùóç áõ-
ôÞ, ç ïðïéáäÞðïôå ôñïðïðïßçóç ôçò ãåíåôéêÞò ðëçñïöï-
ñßáò ìåôáöÝñåôáé êáé óôéò åðüìåíåò ãåíåÝò.
ÐáñÜ ôéò óïâáñÝò ôå÷íéêÝò äõóêïëßåò, ðïõ äõó÷åñáß-
íïõí óçìáíôéêÜ ôçí åöáñìïãÞ ôçò ãïíéäéáêÞò èåñáðåß-
áò, õðÜñ÷ïõí âÜóéìåò åëðßäåò üôé ôá ó÷åôéêÜ ðñïâëÞ-
ìáôá èá îåðåñáóôïýí ìåëëïíôéêÜ êáé ç ãïíéäéáêÞ èå-
ñáðåßá èá áðïôåëÝóåé âáóéêü èåñáðåõôéêü ìÝóï ãéá ôç
ñéæéêÞ áíôéìåôþðéóç ðïëëþí ìïíïãïíéäéáêþí ãåíåôéêþí
íïóçìÜôùí.30–33,51,52
5.3. ÍïõêëåúêÜ ïîÝá
Ç éäÝá ãéá ôç ÷ñçóéìïðïßçóç ôùí íïõêëåúêþí ïîÝùí
ãéá èåñáðåõôéêïýò óêïðïýò ðáñïõóéÜóôçêå Þäç áðü ôç
Å. ÊÁÍÁÂÁÊÇÓ êáé Á. ÎÁÚÄÁÑÁ
äåêáåôßá ôïõ 1970. Áñ÷éêÜ, ÷ñçóéìïðïéÞèçêáí ãéá ôçí
áíáóôïëÞ óýíèåóçò ðáèïëïãéêþí ðñùôåúíþí, äåóìåý-
ïíôáò ìå õâñéäéóìü ôï mRNA ðïõ óõíèÝôåé ôéò ðñùôåÀíåò
áõôÝò. Ðñüóöáôá, ÷ñçóéìïðïéÞèçêáí óõíèåôéêÜ íïõ-
êëåúêÜ ïîÝá (aptamers) ãéá áðåõèåßáò áíáóôïëÞ ôçò ëåé-
ôïõñãéêüôçôáò ôçò ðñùôåÀíçò. Ç ëåéôïõñãßá áõôþí ôùí
íïõêëåúêþí ïîÝùí ìïéÜæåé ìå åêåßíç ôùí ìïíïêëùíéêþí
áíôéóùìÜôùí êáé öáßíåôáé üôé ìåëëïíôéêÜ èá áðïôåëÝóåé
âáóéêü èåñáðåõôéêü ìÝóï ãéá ðïëëÜ íïóÞìáôá.53–55
6. ÓÕÃÊÑÉÔÉÊÇ ÃÏÍÉÄÉÙÌÁÔÉÊÇ
Óôçí ðïñåßá ôçò ÷áñôïãñÜöçóçò ôïõ áíèñþðéíïõ ãï-
íéäéþìáôïò Ýãéíå óáöÞò ç óðïõäáéüôçôá ôçò ðáñÜëëçëçò
áíÜëõóçò ôïõ ãïíéäéþìáôïò Üëëùí ðñüôõðùí ïñãáíé-
óìþí. ¸ôóé, ìÝ÷ñé ôï 1999, ôá ãïíéäéþìáôá ðåñßðïõ 100
ïñãáíéóìþí âñßóêïíôáí õðü áíÜëõóç, åíþ ôï 1995 åß÷å
Þäç ïëïêëçñùèåß ç ÷áñôïãñÜöçóç ãéá ôïí Haemophilus
influenzae êáé ìåñéêþí Üëëùí ïñãáíéóìþí (ðßí. 1).
Ïé áñ÷éêïß óôü÷ïé åíüò ôÝôïéïõ åã÷åéñÞìáôïò Þôáí ç
áíÜðôõîç óôñáôçãéêÞò êáé ôå÷íïëïãßáò, ãéá íá ÷ñçóé-
ìïðïéçèåß óôçí áíÜëõóç ôïõ ãïíéäéþìáôïò ôïõ áíèñþ-
ðïõ. ÅíäéáöÝñïí, åðßóçò, ðáñïõóßáæå êáé ç äõíáôüôç-
ôá êáôáíüçóçò ôùí åîåëéêôéêþí óôü÷ùí ìåôáîý äéáöï-
ñåôéêþí ïñãáíéóìþí. Ç óêÝøç üìùò üôé âáóéêü ÷áñá-
êôçñéóôéêü ôçò âéïëïãßáò áðïôåëåß ôï ãåãïíüò üôé ï ãå-
íåôéêüò êþäéêáò åßíáé êïéíüò ãéá üëïõò ôïõò ïñãáíé-
óìïýò, óå óõíäõáóìü ìå ôï õøçëü ðïóïóôü äéáôÞñç-
óçò ôçò äïìÞò êáé ôçò ëåéôïõñãßáò ôùí ãïíéäßùí êáôÜ
ôçí åîÝëéîç, Ýäùóáí Üëëç Ýìöáóç óôïí êëÜäï ôçò óõ-
ãêñéôéêÞò ãïíéäéùìáôéêÞò.56–59
Ç ÷áñôïãñÜöçóç ôïõ ãïíéäéþìáôïò ðñüôõðùí ïñãá-
íéóìþí ðáñÝ÷åé ðëçñïöïñßåò ãéá ôçí áíáæÞôçóç ãïíé-
äßùí õðåýèõíùí ãéá íïóÞìáôá, ãéá ìïíôÝëá ðïëõãïíé-
äéáêÞò êõñßùò êëçñïíïìéêüôçôáò, êáèþò êáé ãéá ôï Ü-
ìåóï «ðåñéâÜëëïí» ôùí ãïíéäßùí. Ìåëåôþíôáò ôéò ó÷Ý-
óåéò ìåôáîý ãåéôïíéêþí ãïíéäßùí êáé ôïí ôñüðï êëçñï-
íïìéêüôçôáò áõôþí, ëáìâÜíïíôáé ðëçñïöïñßåò ó÷åôéêÜ
ìå ôçí áëëçëåðßäñáóç ôùí ãïíéäßùí êáé ãéá ôï ðþò ïé
áíáäéáôÜîåéò óå ãïíßäéá åßíáé óçìáíôéêÝò, üðùò óôéò äéÜ-
öïñåò ìïñöÝò êáñêßíïõ. Ðñüôõðïé ïñãáíéóìïß, êõñßùò
âïïåéäÞ êáé ðïíôßêéá, ÷ñçóéìïðïéïýíôáé êáé ãéá ôç ìå-
ëÝôç ôçò ðïëõãïíéäéáêÞò êëçñïíïìéêüôçôáò. Óçìáíôéêü
ñüëï óôçí êáôáíüçóç ôçò åðßäñáóçò ðïëëáðëþí ãïíé-
äßùí óôçí Ýêöñáóç åíüò âéïëïãéêïý öáéíüôõðïõ äéá-
äñáìÜôéóáí ïé âéâëéïèÞêåò ãïíéäßùí in vivo (äéáãïíé-
äéáêÜ ðïíôßêéá ðïõ ðåñéÝ÷ïõí ìåãÜëá ôìÞìáôá DNA óå
ôå÷íçôü öïñÝá).
Ôá óôïé÷åßá ðïõ ðñïêýðôïõí áðü ôçí áíÜëõóç ôùí
äéáöüñùí ãïíéäéùìÜôùí êáôá÷ùñïýíôáé óå âÜóåéò äå-
äïìÝíùí (cDNA libraries, EST data-expressed sequenc-
ÁÍÈÑÙÐÉÍÏ ÃÏÍÉÄÉÙÌÁ
ed tags). Äýï âáóéêÜ ðñïãñÜììáôá áíÜëõóçò ôùí äå-
äïìÝíùí áõôþí åßíáé ôá XREFdb êáé DRES.
Óôï XREFdb, ãïíßäéá ðñüôõðùí ïñãáíéóìþí óõãêñß-
íïíôáé ìå ãïíßäéá ðïõ Ý÷ïõí ìåôáëëá÷èåß óå áíèñþðé-
íåò ðáèÞóåéò. Õðïëïãßæåôáé üôé ãéá ðåñßðïõ ôá 2/3 ôùí
ãïíéäßùí ðïõ ó÷åôßæïíôáé ìå äéÜöïñåò íüóïõò õðÜñ÷ïõí
ïìüëïãá óå ðñüôõðïõò ïñãáíéóìïýò. ÊáôÜ óõíÝðåéá, ï-
ðïéáäÞðïôå ðëçñïöïñßá ó÷åôéêÜ ìå ôç äïìÞ, ôç ëåé-
ôïõñãßá êáé ôç èÝóç ãïíéäßùí ðñüôõðùí ïñãáíéóìþí
ìðïñåß íá äéåõêïëýíåé ôç ìåëÝôç ôùí ïìüëïãùí ðñïò
áõôÜ ìåôáëëáãìÝíùí áíèñþðéíùí ãïíéäßùí.60,61
Ôï DRES (Drosophila-Related Expressed Sequences)
åðéôñÝðåé ôïí ðñïóäéïñéóìü áíèñþðéíùí ãïíéäßùí ðïõ
åõèýíïíôáé ãéá ôçí åìöÜíéóç ìåôáëëáãìÝíùí öáéíüôõ-
ðùí óôçí Drosophila. Ðñïêýðôïõí Ýôóé ãïíßäéá õðïøÞ-
öéá ãéá ôï óõó÷åôéóìü ôïõò ìå áíèñþðéíåò ðáèÞóåéò.
ÐïëëÜ üìùò áðü ôá ãïíßäéá ðïõ ÷áñáêôçñßæïíôáé ùò
ïìüëïãá ìåôáîý ôçò Drosophila êáé ôïõ áíèñþðïõ åì-
öáíßæïõí äéáöïñÝò óôç ëåéôïõñãßá ôïõò. Ç óõãêñéôéêÞ
áíÜëõóç êáëåßôáé íá åñìçíåýóåé êáé ôï äéáöïñåôéêü
ôñüðï äñÜóçò üìïéùí ãïíéäßùí. Óôï ðñïóå÷Ýò ìÝëëïí,
Ýíáò Üëëïò ïñãáíéóìüò, ôï zebra-fish, èá ðñïóôåèåß óôá
ðñïãñÜììáôá áíÜëõóçò XREFdb êáé DRES, ìå óêïðü
íá äþóåé ðëçñïöïñßåò ãéá ôçí åìâñõúêÞ áíÜðôõîç ôùí
óðïíäõëùôþí.
Ç ìåëÝôç ðñüôõðùí ïñãáíéóìþí, üðùò ï C. elegans,
âïçèÜåé óôïí ðñïóäéïñéóìü íÝùí ãïíéäßùí êáé áëëç-
ëïõ÷éþí åëÝã÷ïõ, ìÝóù åéäéêþí ðñïãñáììÜôùí ìåëÝôçò
ãïíéäßùí êáé åîïíßùí.
ÅðéðëÝïí, ç óõãêñéôéêÞ áíÜëõóç ôùí ìç êùäéêïðïéç-
ìÝíùí ðåñéï÷þí ôïõ DNA óôïí Üíèñùðï êáé óå ïñãá-
íéóìïýò üðùò ôá ðïíôßêéá, áðÝäåéîå ôï ìåãÜëï âáèìü
äéáôÞñçóçò ôùí áëëçëïõ÷éþí áõôþí êáôÜ ôçí åîÝëéîç.
Óôï ìÝëëïí, ç óýãêñéóç ôùí ðåñéï÷þí áõôþí óôïí Üí-
èñùðï êáé óå åîåëéêôéêÜ ðéï áðïìáêñõóìÝíïõò ïñãá-
íéóìïýò, üðùò ôá êïôüðïõëá êáé ôá øÜñéá, åíäÝ÷åôáé íá
áðïäåé÷èåß ÷ñÞóéìç.62,63
Ç ìåëÝôç ôçò ëåéôïõñãßáò åíüò ãïíéäßïõ ðåñéëáìâÜíåé
êáé ôïí áêñéâÞ êáèïñéóìü ôçò åíôüðéóçò ôïõ ðñïúüíôïò
ôïõ ãïíéäßïõ óôï êýôôáñï. Ôå÷íéêÝò ôÝôïéïõ åßäïõò ÷ñç-
óéìïðïéïýíôáé ãéá ãïíßäéá ðïõ ó÷åôßæïíôáé ìå ôïí êõô-
ôáñéêü êýêëï êáé ôçí êõôôáñéêÞ áýîçóç. Ç óýãêñéóç ôçò
öõóéïëïãéêÞò åíôüðéóçò ìéáò ðñùôåÀíçò ìå ôçí åíôüðé-
óç ìéáò ôå÷íçôÜ áëëïéùìÝíçò (ìåôáëëáãìÝíçò) ðñù-
ôåÀíçò õðïäçëþíåé äéáöïñÝò óå ðñùôåúíéêÝò èÝóåéò á-
ðáñáßôçôåò ãéá ôç ëåéôïõñãßá êáé ôçí åíôüðéóç áõôþí.62,63
Ç ìåëÝôç ðñüôõðùí ïñãáíéóìþí åðåêôÜèçêå êáé óå
ðñïêáñõùôéêïýò ïñãáíéóìïýò ðïõ åõèýíïíôáé ãéá á-
óèÝíåéåò, ð.÷. Helicobacter pylori, Chlamydia pneumo-
481
niae, ìå óêïðü ôçí áíÜðôõîç ðéï åõáßóèçôùí äéáãíù-
óôéêþí åñãáëåßùí êáé ôïí åíôïðéóìü íÝùí óôü÷ùí ãéá
åìâüëéá.
7. ÅÐÉÐÔÙÓÅÉÓ ÔÇÓ ×ÁÑÔÏÃÑÁÖÇÓÇÓ
ÔÏÕ ÁÍÈÑÙÐÉÍÏÕ ÃÏÍÉÄÉÙÌÁÔÏÓ
Ìå ôçí Ýíáñîç ôçò ÷áñôïãñÜöçóçò ôïõ ãïíéäéþìáôïò
êáôÝóôç óáöÞò ç áíÜãêç ðáñÜëëçëçò ìåëÝôçò ôùí çèé-
êþí, íïìéêþí êáé êïéíùíéêþí åðéðôþóåùí, ðïõ ó÷åôß-
æïíôáé ìå ôçí åöáñìïãÞ ôçò íÝáò ôå÷íïëïãßáò óôç ìå-
ëÝôç ôùí ãåíåôéêþí íïóçìÜôùí.
Óôç âÜóç áõôÞ áíáðôý÷èçêå ôï ðñüãñáììá ELSI (Ethi-
cal, Legal, Social Implications), óôï ïðïßï äéáôÝèçêå ôï
5% ðåñßðïõ ôïõ ðñïûðïëïãéóìïý, ìå óêïðü íá ìåëå-
ôÞóåé:8,34,38
– Ôéò äõíáôüôçôåò ÷ñÞóçò êáé áîéïëüãçóçò ôçò ãåíåôé-
êÞò ðëçñïöïñßáò
– Ôç äõíáôüôçôá åöáñìïãÞò ôçò íÝáò ôå÷íïëïãßáò óôçí
êëéíéêÞ ðñÜîç
– Ôéò åðéðôþóåéò ðïõ ìðïñåß íá ðñïêýøïõí áðü ôç ÷ñÞ-
óç ôçò âéïúáôñéêÞò Ýñåõíáò
– Ôéò ðñïûðïèÝóåéò ãéá ôçí åðéìüñöùóç ôùí åðéóôçìü-
íùí õãåßáò êáé ôïõ êïéíïý ãéá ôéò äõíáôüôçôåò êáé ôéò
ðñïïðôéêÝò áðü ôç ÷áñôïãñÜöçóç ôïõ áíèñþðéíïõ ãï-
íéäéþìáôïò
– Ôç ÷ñÞóç ôçò íÝáò ôå÷íïëïãßáò ãéá ìåëÝôç ôçò ãåíå-
ôéêÞò ðïéêéëïìïñößáò áíÜìåóá óå Üôïìá êáé êïéíùíé-
êÝò ïìÜäåò
– Ôïõò ôñüðïõò ìå ôïõò ïðïßïõò öõëåôéêïß, åèíéêïß êáé
ïéêïíïìéêïß ðáñÜãïíôåò åðçñåÜæïõí ôç ÷ñÞóç, ôçí êá-
ôáíüçóç êáé ôçí åñìçíåßá ôçò ãåíåôéêÞò ðëçñïöïñßáò,
ôç ÷ñÞóç ôùí ãåíåôéêþí õðçñåóéþí êáé ãéá ôçí áíÜ-
ðôõîç ôçò ðïëéôéêÞò ðïõ ó÷åôßæåôáé ìå ôï èÝìá áõôü.
Óå ðñáêôéêü åðßðåäï, óÞìåñá Ý÷ïõí ãßíåé ðñïóðÜèåéåò
ãéá ôç èÝóðéóç íïìïèåóßáò êáé ôç äéáìüñöùóç êïéíù-
íéêÞò óõìðåñéöïñÜò, ðïõ óå ìåãÜëï âáèìü åîáóöáëß-
æåé êáé ôçí éäéïêôçóßá ôïõ âéïëïãéêïý õëéêïý êáé ôçí á-
ôïìéêüôçôá ôçò ãåíåôéêÞò ðëçñïöïñßáò ãéá ôçí áðïöõ-
ãÞ ôçò êïéíùíéêÞò äéÜêñéóçò ìå âÜóç ôï ãåíåôéêü õðü-
óôñùìá ôïõ áôüìïõ, ðïõ èá ìðïñïýóå íá äçìéïõñãÞ-
óåé ðñïâëÞìáôá óôçí áóöÜëéóç êáé ôï äéêáßùìá åñãá-
óßáò.
Óå åõñùðáúêü åðßðåäï, ïé óõæçôÞóåéò óôï Óõìâïýëéï
ôçò Åõñþðçò Üñ÷éóáí óôçí áñ÷Þ ôçò äåêáåôßáò ôïõ 1980
óôá ðëáßóéá ìéáò ad hoc åðéôñïðÞò (ÅðéôñïðÞ Âéïçèé-
êÞò) ãéá ôç ìåëÝôç ôùí ðñïâëçìÜôùí ðïõ ó÷åôßæïíôáé ìå
ôçí åöáñìïãÞ ôçò âéïôå÷íïëïãßáò óôïí Üíèñùðï.
482 Å. ÊÁÍÁÂÁÊÇÓ êáé Á. ÎÁÚÄÁÑÁ

Ïé óõæçôÞóåéò áõôÝò êáôÝëçîáí óôçí õðïãñáöÞ óýì-
âáóçò, ôçí ïðïßá õéïèÝôçóå êáé ç ÷þñá ìáò äéÜ íüìïõ
ôï 1998 (Í. 2619/1998).
Ç óýìâáóç áõôÞ, ðïõ áöïñÜ ôï áíèñþðéíï ãïíéäßù-
ìá óôá Üñèñá 11–14, áíáöÝñåôáé óôçí áðáãüñåõóç êÜ-
èå ìïñöÞò äéÜêñéóçò ôïõ áôüìïõ ìå âÜóç ôá ãåíåôéêÜ
ôïõ ÷áñáêôçñéóôéêÜ êáé ôçí åðéëïãÞ ôïõ öýëïõ ãéá ëü-
ãïõò Üëëïõò åêôüò áðü êáèáñÜ éáôñéêïýò. ÁíáöÝñåôáé
åðßóçò óôéò ðáñåìâÜóåéò óôï áíèñþðéíï ãïíéäßùìá, ï-
ñßæïíôáò üôé áõôÝò èá ìðïñïýóáí íá åðéôñáðïýí ìüíï
ãéá ðñïëçðôéêïýò Þ èåñáðåõôéêïýò ëüãïõò êáé ðïôÝ ãéá
áëëáãÞ óôï ãïíéäßùìá ôùí áðïãüíùí ôïõ. ÁíáöÝñåôáé,
ôÝëïò, óôç ÷ñÞóç åñãáóôçñéáêþí åîåôÜóåùí ãéá ðñü-
ëçøç ãåíåôéêÞò íüóïõ óå åðßðåäï öïñÝùí Þ ãéá áíß-
÷íåõóç ãåíåôéêÞò ðñïäéÜèåóçò. Ïé åîåôÜóåéò áõôÝò èá
ðñÝðåé íá ãßíïíôáé ìüíï åöüóïí åßíáé ðñïò üöåëïò ôçò
õãåßáò ôïõ áôüìïõ êáé ìåôÜ áðü êáôÜëëçëç ãåíåôéêÞ óõì-
âïõëåõôéêÞ.64,65

ABSTRACT

Ôhe human genome project

E. KANAVAKIS, A. XAIDARA
Medical Genetics, University of Athens,
“Agia Sophia” Children’s Hospital, Athens, Greece
Archives of Hellenic Medicine 2001, 18(5):475–484

Mapping the human genome is considered to be the most important development in biology with great im-
plications for medical science. The goal of the Human Genome Project is to sequence the entire human
genome, which contains the whole genetic information. The human genome consists of 3 billion base pairs of
DNA which are distributed among 24 distinct chromosomes, 22 autosomes and 2 sex chromosomes. Within
this vast array of nucleotides is encoded an estimated 50,000 to 100,000 genes and the necessary elements
controlling the regulation of their expression. The coding portions of genes represent 2–3% of human DNA.
The human genome is characteristic for humans but it is not unique, since the sequence of a normal allele
differs from one or more polymorphic alleles by changes affecting the DNA sequence. The Human Genome
Project was officially begun in 1990 by the academic research community and was accelerated in 1998 by the
efforts of private corporations. The results of both parts were announced in common in June 2000. In Febru-
ary 2001, each sector reported update data with its own separate publication. Applications of genetic knowl-
edge have a broad impact on both diagnosis and treatment. Genetic diagnosis is used for prevention of ge-
netic diseases by means of either prenatal of preclinical presymptomatic diagnosis. Approximately 1,000 ge-
netic diseases have already been studied and the gene responsible for them have been cloned. Genetic tests
are now available for disorders which have lower penetrance or later onset and for which there are available
limited interventions and inadequate or no treatment. Genetic tests can identify those who are affected with
genetic diseases but also those who are healthy carriers of disorders or have the genetic predisposion to de-
velop a disease if exposed to a specific environmental factor. Knowing the genetic information can prevent or
delay the development of the disease or result in the better course and prognosis of the disease. As far as ther-
apeutic intervention is concerned, medicines tailored in specific genes and the ongoing research in gene or
nucleic acids therapy will lead to diminished drug side effects and permit better or permanent disease control.
Comparative genomics assists in better understanding of the gene environment and helps in identifying genes
responsible for multifactorial diseases. It is obvious that the application of the knowledge obtained by the Hu-
man Genome Project raises ethical, legal and social issues. The goal of the study of the potential benefits and
adverse consequences is to create legislation and public policies which will set the framework for assertion of
autonomy, consent, privacy and ownership of the genetic information, protection from stigmatization, dis-
crimination or modification of human relationships, and justification of the human interests and human rights.

Key words:: DNA sequence, Genes, Genetics, Human genome, Polymorphisms

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Corresponding author:
Å. Kanavakis, Medical Genetics, “Aghia Sophia” Children’s Hos-
pital, Athens, Greece