Hva\u00f0 \u00fe\u00fd\u00f0ir \u00fea\u00f0 a\u00f0 erf\u00f0av\u00edsar s\u00e9u \u00f3n\u00fdtir og hafa \u00feeir \u00e1hrif \u00e1 svipfar? Gen (erf\u00f0av\u00edsar) eru mikilv\u00e6gasti hluti erf\u00f0aefnisins. Erf\u00f0aefni\u00f0 DNA eru tv\u00ed\u00fe\u00e1tta \u00fer\u00e6\u00f0ir sem mynda litningana. Vi\u00f0 manneskjurnar f\u00e1um eitt sett af litningum fr\u00e1 m\u00f3\u00f0ur og eitt sett fr\u00e1 f\u00f6\u00f0ur. \u00dev\u00ed h\u00f6fum vi\u00f0 tv\u00f6 heil eint\u00f6k af flestum okkar genum - eitt fr\u00e1 hvoru foreldri. \u00dea\u00f0 er kalla\u00f0 a\u00f0 vera tv\u00edlitna. Algengast er a\u00f0 d\u00fdr s\u00e9u tv\u00edlitna en bakter\u00edur eru flestar einlitna. Arnar P\u00e1lsson. \u201eHva\u00f0 \u00fe\u00fd\u00f0ir \u00fea\u00f0 a\u00f0 erf\u00f0av\u00edsar s\u00e9u \u00f3n\u00fdtir og hvernig kemur sl\u00edkt fram \u00ed svipger\u00f0 f\u00f3lks?\u201c. V\u00edsindavefurinn 4.5.2015. http:\/\/visindavefur.is\/?id=69712. St\u00f6kkbreytingar eru fr\u00e1vik \u00ed erf\u00f0aefninu. \u00de\u00e6r geta mynda\u00f0 n\u00fdjar \u00fatg\u00e1fa af geni (oft au\u00f0kennt sem a) - mi\u00f0a\u00f0 vi\u00f0 upprunalegu (forfe\u00f0ra) \u00fatg\u00e1funa (au\u00f0kennt sem A). \u00c1 me\u00f0an a er f\u00e1t\u00ed\u00f0 \u00ed stofninum, finnst h\u00fan n\u00e6r eing\u00f6ngu \u00ed einstaklingum me\u00f0 Aa arfger\u00f0. Ef a ver\u00f0ur algengari aukast l\u00edkurnar \u00e1 a\u00f0 aa einstaklingar ver\u00f0i til. \u00cd l\u00edfverum finnst heilmikill erf\u00f0abreytileiki sem er upprunalega af v\u00f6ldum st\u00f6kkbreytinga. St\u00f6kkbreytingar m\u00e1 flokka eftir m\u00f6gulegum \u00e1hrifum \u00e1 h\u00e6fni l\u00edfvera. \u00de\u00e6r geta veri\u00f0 ska\u00f0legar, hlutlausar e\u00f0a j\u00e1kv\u00e6\u00f0ar. J\u00e1kv\u00e6\u00f0ar breytingar eru hr\u00e1efni fyrir n\u00e1tt\u00farulegt val en hlutlausar breytingar hafa engin \u00e1hrif. Ska\u00f0legar breytingar draga hins vegar \u00far l\u00edfsl\u00edkum e\u00f0a frj\u00f3semi, oftast vegna \u00feess a\u00f0 \u00fe\u00e6r ey\u00f0ileggja gen e\u00f0a raska virkni \u00feeirra. Til a\u00f0 vita hvernig gen skemmast \u00feurfum a\u00f0 vi\u00f0 a\u00f0 skilja uppbyggingu \u00feeirra. Gen eru samsett \u00far \u00f3l\u00edkum hlutum, til d\u00e6mis stj\u00f3rnr\u00f6\u00f0um og t\u00e1knr\u00f6\u00f0um. \u00de\u00e6r s\u00ed\u00f0ast t\u00f6ldu skr\u00e1 fyrir hlutum pr\u00f3t\u00edns sem geni\u00f0 er forskrift a\u00f0. Punktbreytingar lei\u00f0a til skipta \u00e1 st\u00f6kum b\u00f6sum (DNA er samsett \u00far A, C, G og T b\u00f6sum). Punktbreyting \u00e1 basa \u00ed mikilv\u00e6gum hluta gens, getur ey\u00f0ilagt \u00fea\u00f0. Einnig eru \u00feekktar \u00farfellingar og innskot \u00e1 b\u00f6sum e\u00f0a jafnvel brot og tilflutningur \u00e1 litningab\u00fatum (litningabreytingar). Ef breyting fellir \u00fat hluta gens e\u00f0a lei\u00f0ir til skipta \u00e1 mikilv\u00e6gri am\u00edn\u00f3s\u00fdru, getur \u00fea\u00f0 haft alvarleg \u00e1hrif og jafnvel \u00f3virkja\u00f0 pr\u00f3t\u00edn-afur\u00f0 gensins. Segja m\u00e1 a\u00f0 sl\u00edk gen s\u00e9u \u00f3n\u00fdt. A\u00f0rar st\u00f6kkbreytingar eru v\u00e6gari. Gen geta \u00fev\u00ed skemmst \u00e1 \u00f3tal vegu, og mismiki\u00f0. \u00dea\u00f0 veltur \u00e1 erf\u00f0afr\u00e6\u00f0ilegum og \u00fer\u00f3unarfr\u00e6\u00f0ilegum l\u00f6gm\u00e1lum hva\u00f0a \u00e1hrif \u00f3n\u00fdt gen hafa \u00e1 svipfar (svipfar e\u00f0a svipger\u00f0 er safn allra einkenna einstaklings). Ma\u00f0urinn hefur um 20.000 gen sem hvert um sig gegna \u00f3l\u00edkum hlutverkum. Sum gen eru nau\u00f0synleg \u00ed \u00f6llum frumum l\u00edkamans, \u00e1 me\u00f0an \u00f6nnur eru s\u00e9rh\u00e6f\u00f0ari (til d\u00e6mis bara notu\u00f0 \u00ed h\u00fa\u00f0 e\u00f0a munnvatnskirtlum). Erf\u00f0abreytileiki \u00ed einu geni hefur ekki s\u00f6mu \u00e1hrif og erf\u00f0abreytileiki \u00ed \u00f6\u00f0ru geni. L\u00edfvera kann a\u00f0 lifa af \u00e1n gens sem framlei\u00f0ir munnvatnsens\u00edm, en ekki \u00e1n gens nau\u00f0synlegt \u00f6llum frumum l\u00edkamans. Vi\u00f0 erum \u00f6ll me\u00f0 margar ska\u00f0legar breytingar, \u00e1 arfblendnu \u00e1standi. Ef vi\u00f0 fengum til d\u00e6mis \u00f3n\u00fdtt eintak af geni X fr\u00e1 pabba, en heilt eintak fr\u00e1 m\u00f6mmu, \u00fe\u00e1 erum vi\u00f0 arfblendin (Xx). S\u00fa sta\u00f0reynd a\u00f0 vi\u00f0 erum tv\u00edlitna veitir okkur vernd fyrir \u00f3n\u00fdtum genum. \u00deetta er kalla\u00f0 erf\u00f0abyr\u00f0in (e. genetic load) sem vi\u00f0 berum \u00f6ll. Erf\u00f0abyr\u00f0in veldur \u00fev\u00ed a\u00f0 \u00ed hverri kynsl\u00f3\u00f0 geta runni\u00f0 saman kynfrumur me\u00f0 ska\u00f0legar breytingar \u00ed sama geni. Ef geni\u00f0 er mj\u00f6g mikilv\u00e6gt og st\u00f6kkbreytingin ska\u00f0leg, aukast l\u00edkur \u00e1 f\u00f3sturl\u00e1ti. \u00cd \u00f6\u00f0rum tilfellum \u00feroskast vi\u00f0komandi a\u00f0 \u00fev\u00ed er vir\u00f0ist e\u00f0lilega \u00fer\u00e1tt fyrir a\u00f0 vera arfhreinn um galla\u00f0 gen, en \u00fej\u00e1ist ef til vill af sj\u00fakd\u00f3mi s\u00ed\u00f0ar \u00e1 l\u00edfslei\u00f0inni. \u00cd enn \u00f6\u00f0rum tilfellum hefur \u00fea\u00f0 engin \u00e1hrif ef einstaklingurinn er arfhreinn um \u00f3n\u00fdtt gen. Ranns\u00f3knir \u00e1 bakter\u00edum, gersveppum og flugum hafa s\u00fdnt a\u00f0 ekki eru \u00f6ll gen l\u00edfsnau\u00f0synleg. Gersveppur getur til d\u00e6mis lifa\u00f0 \u00e1g\u00e6tu l\u00edfi \u00ed r\u00e6kt, \u00feegar hann er arfhreinn um \u00farfellingu \u00e1 heilu geni. Reyndar eru innan vi\u00f0 10% af genum sveppsins l\u00edfsnau\u00f0synleg. N\u00fdleg ranns\u00f3kn \u00cdslenskrar erf\u00f0agreiningar s\u00fdndi a\u00f0 um 8% \u00cdslendinga eru arfhreinir um sk\u00f6ddu\u00f0 e\u00f0a \u201e\u00f3n\u00fdt\u201d gen. Genin sem um r\u00e6\u00f0ir eru um 6% af erf\u00f0amengi okkar, um 1200 gen \u00ed allt. Algengast er a\u00f0 finna galla \u00ed lyktavi\u00f0takagenum, sem er reyndar einnig algengt me\u00f0al \u00e6ttingja okkar \u00ed apar\u00edkinu. H\u00e9r vir\u00f0ist felast m\u00f3ts\u00f6gn. Hv\u00ed hefur ma\u00f0urinn (e\u00f0a sveppurinn) \u00e1kve\u00f0i\u00f0 gen ef hann getur lifa\u00f0 \u00e1n \u00feess? Erf\u00f0afr\u00e6\u00f0in og \u00fer\u00f3unarfr\u00e6\u00f0in hefur nokkrar \u00fatsk\u00fdringar \u00e1 svona fyrirb\u00e6rum. \u00cd fyrsta lagi er s\u00fdnd (e. penetrance) gena og erf\u00f0abreytileika misj\u00f6fn. Tveir einstaklingar me\u00f0 s\u00f6mu erf\u00f0asamsetningu (til d\u00e6mis arfhreinir um skadda\u00f0 gen aa), f\u00e1 ekki endilega s\u00f6mu svipger\u00f0. \u00cd \u00f6\u00f0ru lagi er tj\u00e1ning (e. expressivity) arfger\u00f0a ekki alltaf s\u00fa sama. Tveir einstaklingar me\u00f0 s\u00f6mu erf\u00f0asamsetningu f\u00e1 ekki alltaf jafnsterk einkenni. \u00deri\u00f0ja \u00fatsk\u00fdringin er s\u00fa a\u00f0 sum gen eru skyld, og geta hj\u00e1lpast a\u00f0. Ef eitt gen er galla\u00f0, getur n\u00e6rskylt gen stundum leyst hlutverk \u00feess n\u00e6gilega vel. \u00cd fj\u00f3r\u00f0a lagi getur veri\u00f0 a\u00f0 vi\u00f0komandi gen s\u00e9u ekki mikilv\u00e6g vi\u00f0 allar a\u00f0st\u00e6\u00f0ur, til d\u00e6mis bara \u00ed h\u00f6r\u00f0u \u00e1ri e\u00f0a \u00feegar \u00e1kve\u00f0i\u00f0 sn\u00edkjud\u00fdr e\u00f0a pest herjar. A\u00f0 endingu m\u00e1 segja a\u00f0 l\u00f6gm\u00e1l erf\u00f0a og \u00fer\u00f3unar, og samspil tilviljana, erf\u00f0a og umhverfis geti \u00fatsk\u00fdrt af hverju sumir geta lifa\u00f0 \u00e1g\u00e6tu l\u00edfi me\u00f0 \u00f3n\u00fdt gen. Samantekt: \u00d3n\u00fdt gen eru vegna st\u00f6kkbreytinga sem ey\u00f0ileggja mikilv\u00e6ga hluta gena. Sl\u00edkar st\u00f6kkbreytingar geta \u00e1 arfhreinu formi valdi\u00f0 dau\u00f0a e\u00f0a sj\u00fakd\u00f3mum. Stundum lifir f\u00f3lk g\u00f3\u00f0u l\u00edfi \u00fer\u00e1tt fyrir a\u00f0 vera arfhreint um g\u00f6llu\u00f0 gen. \u00c1st\u00e6\u00f0ur \u00feess eru margar, til d\u00e6mis bygging gena, skyldleiki gena, \u00f3l\u00edkt mikilv\u00e6gi gena og heppni. S\u00fa sta\u00f0reynd a\u00f0 vi\u00f0 erum tv\u00edlitna veitir okkur vernd fyrir \u00f3n\u00fdtum genum. \u00a0 Heimildir og mynd: Gu\u00f0mundur Eggertsson.Hver er munurinn \u00e1 erf\u00f0agalla og erf\u00f0asj\u00fakd\u00f3mi? V\u00edsindavefurinn, 20.11.2002. Gu\u00f0mundur Eggertsson. Af hverju ver\u00f0a st\u00f6kkbreytingar? V\u00edsindavefurinn, 13.8.2003. Winzeler EA, Shoemaker DD og 50 a\u00f0rir. Functional characterization of the S. cerevisiae genome by gene deletion and parallel analysis. Science. 1999 Aug 6;285(5429):901-6. Patrick Sulem, Hannes Helgason, og 17 a\u00f0rir. Identification of a large set of rare complete human knockouts. Nature Genetics, 2015 doi:10.1038\/ng.3243<\/p>\n","protected":false},"excerpt":{"rendered":"
Hva\u00f0 \u00fe\u00fd\u00f0ir \u00fea\u00f0 a\u00f0 erf\u00f0av\u00edsar s\u00e9u \u00f3n\u00fdtir og hafa \u00feeir \u00e1hrif \u00e1 svipfar? Gen (erf\u00f0av\u00edsar) eru mikilv\u00e6gasti hluti erf\u00f0aefnisins. Erf\u00f0aefni\u00f0 DNA eru tv\u00ed\u00fe\u00e1tta \u00fer\u00e6\u00f0ir sem mynda litningana. Vi\u00f0 manneskjurnar f\u00e1um eitt sett af litningum fr\u00e1 m\u00f3\u00f0ur og eitt sett fr\u00e1 … Halda \u00e1fram a\u00f0 lesa