G???????? ?????G??F?S? ??? G???????? T???????

1
G???????? ?????G??F?S? ??? G???????? T???????

• ?G??? ??????
• ?????G?S
• ??G?S????? ???????G???S ??????S
• ??????????????? ???????G??? ???????
• ??????? S???? ??????S?????? ?T??O?
• G????? ??S??????? ?T??O? ????????????

2
G???????? ?????G??F?S? ? ???????? ???
G?????O????S

• ?a????sµ?? t?? ??s??
• t?? ????d??? sta ???µ?s?µata.

3
???µ?s?µa 21
4
G???????? ?????G??F?S? ??T???? ?????G??F?S?S

• Ge?et??? ?a?t????f?s?
• F?s??? ?a?t????f?s?

5
G???????? ?????G??F?S?G??????? ?????G??F?S?

• Morgan
• ?????G??F?S? G?????O? ??? ???G?O???????? ??? ??
  F???????? ???S
• ????????? ?? ?????G??F?S? ???S G??????? ?O??S ??
  ????? G?OS?? ? ???????G?? ? ?????????? ?O? ??S?O?
  ???
• ???OS? ??? ???S?????S??S

6
G???????? ?????G??F?S?G??????? ?????G??F?S?

• ???? ??S? ??? G?????O? ?? ????F???????
  ?????????? ???? ??? ???????? ??S ???OS?S
• S?????? T?S? G?????O?A??S
• ????G???????S ??????S
• G?????? OS ??????S
• ?? ?????????S ?????G??F?S?

7
G??????? S????S?

• ??S? ??? G?????O? ?? ??? ???S??????????? ???? ???
  ???????? ??S ???OS?S
• ????????? ?? ??????T?? ? G??????? ???S??S? ??????
  ??? G?????O?
• ??? G?????? ??? ???S?????? S?? ???? ??O??SO??
  ??? S????????? ??????????

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?????? S????S?S- Morgans

• ??a µ???da - Morgan ?e?et???? s??des??
  a?t?st???e? se t?t??a ap?stas? st? ???µ?s?µa p??
  ?a ep?t??pe? ??a? a?as??d?asµ? st? pe????? a?t?
  ?at? t? d????e?a t?? µe??s??.
• 1 Morgan 100 p??a??t?ta a?as??d?asµ?? st??
  ap?stas? a?t?
• centiMorgan (cM) 1 p??a??t?ta a?as??d?asµ??
• 1 ???µ?s?µa ??e? µ???? pe??p?? 100 - 300 c? (1-3
  a?as??d?asµ?? a?? ???µ?s?µa)

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?????? S????S?S

• ?????G?S??S S????S ??T??????O? S????S?S ??????
  ??? ???O?
• ???F???????S ????S ??? ?
• ?0.00 ?a???a? a?as??d?asµ??
• ?0.50 t??a??? d?a????sµ??
• ?gt0.50 µ? s??des? t?? d?? t?p??
• ? ???????µ?? t?? p?????? a?t?? t?? d?? t?µ??
  ???µ??eta? ???????µ?? t?? p??a??t?t?? LOD
  (logarithm of odds) score (Z)
• LOD 3 a?t?st???e? se p??a??t?ta s??des??
  10001 ?a? ? t?µ? t?? ? st?? ?p??a a?t?st???e? ?
  µe?a??te?? t?µ? t?? LOD a?t?p??s?pe?e? t??
  ?e?et??? ap?stas? µeta?? t?? d?? t?p??

10
(No Transcript)
11
Csh x CcShsh
the c and sh loci are said to be 2.8 cM apart.
12
DNA ??????S ??????T?S? ???????F???? (???
?????????F? ???????S???).

• ????µ??f?sµ?? µ????? ??a?sµat?? e? pe?????sµ??
  restriction fragment length polymorphisms (RFLPs)
• ????µ??f?sµ?? e??? ?????e?t?d???
• single nucleotide polymorphisms (SNPs).
• T?se?? st? ????d??µa p?? d?af????? ap? ?t?µ? se
  ?t?µ?.
• 1.42 e?at?µµ???a SNPs st? a????p??? ????d??µa,
  (100 000 ????? sa? ap?t??esµa RFLP (SNP Group,
  2001).
• ????µ??f?sµ?? µ????? ????d?a??? a????????a?
• simple sequence length polymorphisms (SSLPs)
• ?e?????? d?af??et???? µ????? e?a?t?a? t??
  d?af??et???? a???µ?? epa?a?aµßa??µe???
  a?????????? p?? pe???aµß?????

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DNA ??????S

• ?????d???f????? DNA
• 1030 a?t???afa epa?a?aµßa??µe???
  a????????a? µ????? s?????? 4 ß?se?? (6.5 105
  st? a????p??? ????d??µa)
• PCR a????s?
• ?a?????? ?ata??µ? st? ????d??µa
• ????d???f????? DNA
• ?e???? µ??e???
• ?? ?a?????? ?ata??µ? (?????? sta te??µe??)

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S????? S?????? ?? ??? G??????? ???S??S?

• ? G??????? ???S??S? ??? ? F?S??? ???S??S? ???
  ????? ?? ????S
• ? S???????? ?O? ???S?????S?O? ???? ??? O?G???S?
  ????? ???F??????? ??? ??? S???????? ?O?
  ???S?????S?O? ???? ??? S???????G???S?

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F?S??? ?????G??F?S?

• ????T???? ?? G?????? S? S?G????????? T?S? ????
  ????S ?O? ??O??SO???O?

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??T?????G??S F?S???S ?????G??F?S?S??O??SO????
??????S? ?????????O? ?? ?????S? ???????O?
????????O? S???O? (CELL HYBRIDS)

• S?????? ??????O? ???? ?a? ??????O? ?????
• ?????G? ???????O? ??????O?
• (?????G? ??? )
• ???????G?? S??T??O? ???????O? S???O?
• ?????G??F?S? S?G?????????S ??????????S ?? PCR ?
  ??????S?? ???? SOUTHERN

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(No Transcript)
18
??T?????G??S F?S???S ?????G??F?S?S??????S??S
??O??SO???O? IN SITU?? FT???S?? (FISH)

• ????????? ??? ???????? ?????G??F?S? ??? ?????? S?
  ??? ??O??SO??
• ????F?S??? ??O??SO???? (2-10Mb)
• ???????F?S??? ??O??SO???? (1-2Mb)
• ??S?F?S??? ??O??SO???? (50-500kb)
• ??????? ????????T???? ?????? ??O??????S ? G?????
  DNA ???????????? ??? ???G???? ???????F???S?S(5-500
  kb)

19
(No Transcript)
20
(No Transcript)
21
??T?????G??S F?S???S ?????G??F?S?S????O??S??S
??O??SO???O? ?? ????????????? ???S

• ????O??S??S ??S?? ??G?T??S
• S?????? ??S?S?? GC
• ??????S? ?? ??????OS? ?????O?
• (DOT BLOTTING),
• ???S??O?? ???????S? ??S ????????S?S
• (PCR)
• ???????G?? ??????T??O?

22
??T?????G??S F?S???S ?????G??F?S?S?????G??F?S?
?? ???????S????S ???????????S?S

• ?????G??F?S? T?S?O? ???G?O??S?S S?G????????O?
  ???????????SO? ???????S???
• ????? ??G?T?S
• ????? ?????????????

23
??T?????G??S F?S???S ?????G??F?S?S???????G??
??O?O?

• ?????? ???? ?? ?????? ???????S???
• ???S? ???????S???O? ?????O? ????S ?? ?????
  S?????? ???T?? T?SO? (Not I)
• ??S?GOG? ??? ???????????? DNA S? F????S ???
  ???????G?? ??O?O?

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??T?????G??S F?S???S ?????G??F?S?S ?????G??F?S?
?????????S ??O?O?

• ??O??SO???? ?????????S? (CHROMOSOME WALKING)
• ?????S ????G??F? ??????????S ?O? ????????O?
  ??????O?
• (SHOTGUN SEQUENCING)

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(No Transcript)
26
??T?????G??S F?S???S ?????G??F?S?S ?????G??F?S?
M? S???S????S T?S??S ??????????S STS mapping

• STS (sequence tagged sites)
• ???F?????? S? ??? ????? ??????? ??? G???????
  (0,2-0,5 kb) G?? ??? ????? ???? ???????T?? ??????
  ??????S?? PCR ?? ??S? ??? ?????????? ???S
  ?????????? ???G??S ???????O?

27
(No Transcript)
28
??T?????G??S F?S???S ?????G??F?S?S??T????
??????S??? G?????O?

• ESTs (expressed sequence tags)
• ??T???S ??G????S?S G?????O?
• ??????OS? ??????S??? ?????????O? ??????
  ???F??????O? ???O?
• (ZOO BLOTTING)

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Human Genome Project

• ???????G?? ????????O? G??????O? ??? F?S??O?
  ????O? ??? ??T?O????? G?????O????S ??TOS ??? ???
  G?????O????S ???O? ??G???S?O?
• ??T???S??S ???S ??S ??????????S ??? ??T?O?????
  G?????O????S

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?F????G?S ??S ?????G??F?S?S ??? ??T?O?????
G?????O????S

• ?????G??F?S? ??? ??O??????S? G?????O? ????T??O?
  G?? ??? ??F???S? ?ST????O?
• ???G??S G?? ??? ?????? G???????? ?????T??? S???
  ???????? ?ST????O?
• ?????F????S G?? ???S?????? ????G????O? ??
  G??????? ??S?

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G???????? T???????

• ???F?????? S? ??? S????? ??????O? ??? ????? S??
  S???? ??? ???????TOS? ?????O?????O? G?????O? ???
  ????? ????T??? G?? ??? ??F???S? ??S????O?

32
???? ??S G????????S T???????S

• ????????S??S? ??? ?????O??????? G??????? ?? ???
  F?S????G??? G??????
• ?? F?S????G??? G?????? ????F?????? ??? ???? F????
  S?? ??????? S?????S ??? ?ST???
• ??? S???T?????S F????S
• G??????? ???????G????S ??S

33
??? - F????S

• ???????? ????? A ???????G?? ????O??? DNA ??
  ??S? ?? RNA-G?????O?? ???S ?? ????G??F? ????
  ??????? ?? ??SO???OT??? S?? ??O??SO???? ?O?
  ??????O? ??? ????S??
• A??????? ????? A ?? G?????O?? ????O??? DNA
  ????????? ???????S????S ??? G?S??????????S
  ????O???S
• ??????????O????? ??? ????? ? ?? ??????O?? DNA
  ??S?G?? ?? G?????O?? ??? S? S?G????????? T?S? S??
  ??O??SO?? 19
• ??S ??? ???? ?? G?????O?? ????O??? DNA ? ?????S
  ???S?????? ?? ??????? ???????

34
?? ????? S?S?????? F???O?

• ???S? ?????? ??? F?S????G???? DNA S?? ???????
  S?????S
• -S?G??????????S ?????S ?S?O?
• -??G??? ??S?S???? DNA (?????? S????S?).
• ????SO???? ?? ??????? ?????? ??? ??????? ??
  ????S??? ?? T?????????? ??S? ??? ?? ???????? ?O?
  ??????O? S???O?.

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??????S??? G????????S T???????S

• ??S?GOG? ??? F?S????G???? G??????? S? ?????? T?S?
  S?? G?????O??
• ????????S??S? ??? ?????O??????? G??????? ?? ??
  F?S????G??? ?? ?????G? ???S?????S??
• ???????TOS? ??? ?????O??????? G??????? ??
  ?????????? ????????? ??? ???? S?? ???????S?? ???
  ?????F??? ??S F?S????G???S ???????G??S ???
  G???????
• ????G? ??? ?????? ???G??? ??F??S?S ??? G???????

36
(No Transcript)
37
G???????? T??????? ??? ???S????S?? S?????

• ??? ??????? ???S??? ?G???S? ?O??S?S ????????S G??
  G???????? T???????.
• ???S ?? ???S??T???S ?????????? S? ???????????
  ??????? ??? ? ???????? ?O? ??????O? ?????O? ?????
  ???????S????

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???S???????? ????G????S G?? ??? ?????? ?F????G?
??S G????????S T???????S

• ?????S ?????S ?O?S ?O? ??????O? S?? ????? ????
  ??SO???OT?? ?? T?????????? ????? DNA
• ?????????? ??? ?? ???S? ?O? OS F????S ???
  T??????????? DNA
• ???S???G??? ??????S? ??? ?ST???
• 1999, ??????? ?????? 18-???S ??T??? ???
  ??????G????? ?????????? 4 ?????S ???? ??? ??????
  ??S T???????S G?? ??????? OTCD
• 2002 2003, G????? ?????? ??? S?????????? S?
  ??????? ?????? ????????? ?????????
• Gene therapy for treating children with X-SCID
  (sever combined immunodeficiency) or the "bubble
  boy" disease is stopped in France when the
  treatment causes leukemia in one of the patients.
  See 'Miracle' gene therapy trial halted at
  NewScientist.com (October 3, 2002).
• ??S????? S??? ?F????G? ??S G????????S T???????S
  S?? ????????G?????? ??S????? (???????? ??S?????,
  ??T????S, ???????S, ??S?S ALZHEIMER)

39
???SF??? ??????G???? S??? ????? ??S G????????S
T???????S

• ????F??? G?????O? S?? ??????? ??????? ???
  ?G??F???? ?? ?? ???S? ????SO???O? ?????????O? ??
  PEG ??? ?????????? ??? ???????G??F????? F??G??
• S???????? ???? G?? ??? T??????? ??S ??S??
  PARKINSON NewScientist.com (March 20, 2003).
• ?F????G? ??S ????????S ????O? ????O?O? ????A?O?
  RNA (short interfering RNAssiRNAs) NA ??????????
  ??? ??F??S? ?????O?????O? G?????O?
• ??S?S Huntington's at NewScientist.com (March 13,
  2003).
• ???S??T??? ???????G??S ???S ???????? ??O??SO????S
  47?? (artificial human)S?? ??????? S?????S.