• Non ci sono risultati.

Analisi genetica nella sindrome di Ullrich-Turner

N/A
N/A
Protected

Academic year: 2021

Condividi "Analisi genetica nella sindrome di Ullrich-Turner"

Copied!
66
0
0

Testo completo

(1)ALMA MATER STUDIORUM - UNIVERSITA’ DI BOLOGNA. Facoltà di Medicina e Chirurgia DOTTORATO DI RICERCA IN FISIOPATOLOGIA DELLO SVILUPPO SESSUALE XIX CICLO Coordinatore: Prof. Gian Paolo Salvioli. ANALISI GENETICA NELLA SINDROME DI ULLRICH-TURNER. Tesi di Dottorato. Dottoranda:. Relatore:. Dr.ssa Nicoletti Annalisa. Chiar.mo Prof. Alessandro Cicognani. Correlatore: Chiar.ma Prof. Laura Mazzanti. ANNO ACCADEMICO 2005-2006.

(2) A Ugo e Mary.

(3)  .   .

(4)     .   . .  . ).  . !"#$ %.  . & '!  (&

(5) "

(6) $ .  ). *##$  +.  . , -  %.  .. !,  /. 

(7)  & 

(8)   ) ). 0  ). ). #0  . )). '  . ). 10#0  +. ).. 2#21#3045). !, + )+. & )/. )6. ###  ).  &

(9) 

(10)  ). . #$$)  ).. . & )%. ). !,  . ..  '  . +.  

(11)

(12) 7  .. 6. ( (& !8   ...

(13)  .

(14) .  9# # :   4# ;  +  20     :;

(15) <  # 2##       2 =#  #;2:  (4#'$  $)<   #2 4=  2#0    #$<>#=.?#2#==0  4#  2 #  4@  # ## # # #0  20 : == #  # 1   # #2#  2  !,A # )  # 20< : 2#=#@#-B-2C >#4#=<&<, - #-$<#2#A #>##04#)   !,<   #2  = 4 ##0   # 1   , - > # #    #  A   2000 4# )  !, : # 2##@ 4@0 ## 2  2 #  2##@  0  #1##@@1<## 2#2## 2 4@0   2   22< : #    11  10   210  #<  <D=#20. . .

(16)  .   .    

(17)    &   :;

(18)  B

(19) C >   2E  B # .//C  #:< 00   B .<-  ..?C  20 ##0   # - B +<-<B-CA +<-<B-CA +<-<B-C 2E1C 1##<#2#2E    11 2< 00 4  )/?  #22## - <    20   2#  2 4  # - B#. +<-<B-C" .<-C    .?< . <   .<- 2 #    +<--<  1 .?;/?#>2#1#$ B .<-" +<-$CFGF G.  12 2#  = =@H<   # # #2 2# 1 < @## #  ##  &

(20) @  ##  #: 12:  

(21)   = 2. .

(22)    ! . .  . . "!. #$%. F G. . &'% F G. !(). #%. F G. (*!. +,% F G. -!. ,,%. F G. *. &&% F G. *. &%. F)G. .. '% F G. .. ,% F G ,'% F G. /)0!  ,% F)G. . 2 #%. F)G. !..!-. !( & %. F)G. .-(.&,% F G. . 0-. (1. . . &2% F G. 0 

(23) ** . . >#

(24) <#/?# 2I2##<2=#2#=<11D#=22  2D    22<   #: 22  >2#*#2-2 & # 2I ## 2  #  0  2 1  #  #  <  2I ==   #  =0   # #  # 1 B#02C22 ==410##1>  # 2  2  #  4#0  21H4H  4# 2 >#= 2 #FG . . ).

(25)   

(26) 

(27) 

(28)   & # 40 # 2  

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

(30) @<  2 #  # ;  

(31)  #  #40   #2#@  #: 12:  ## 9  #:   # 2    #: 1#:  

(32)  #   &42# > :  12  

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

(34) 4#A2#0#-B-C2I  #:  =    #: 12: 2:A 1  2#0       # $ 1##:@#

(35) = # @#  2  > 2##@ 1  # 2=#12<2 .<-:2<  2. .<-" +<--   220  . +<--. 2##=#: FG#2  #@  =0    #21    #:    12  

(36)  > 4  < == 4#2## 110     # 4 2  #F G.  #  # #   #  2 : #22=<###### # =1 #  # +<--A  # +<-$  # - > #2   <  # .<- 2I ## # 2 :  9# 2 :  

(37)  #     2@@   1# ###< 2## #@ 4 0 4#2##  #. .<-  # #  . 14=0#-<:# +<--2  #0   B C    #     # -<       ### #  # +<-$A# .<-#2#->== 2 4=0<  # 22  # - = = 2#<  #   2  # 1 2@@ ## 2  0  # # 2#   #  

(38)  .<-  #<  #2=02#0"#:# #11 2  0    #2##<  : ##@#2012 422 #;  

(39)  >  ##0  2##2<#2##@D =0##<2:J##  +.

(40) 2  =0  # : 2 200   2 200 8 # =# 2##< 4 #  2  =#   23  0  2   # B@ '  ! #   ./ 1#C  =2212B2#0 8 ,C<#D##A=0 #0#$&2@:# #

(41) ###2  2 ##  @#  # ###<  # ##     #:  @# B 6  )/? #2  220#2#=D#$C> #==2##   #  =0 ;  

(42)  >  #   =D   22 2  2##@D : #  2## 11 = #2 2 2 1:< 2=0   1 2# =<  2    D  =&#:2=# #3@###A4#110=A@# : ##   1 2 4#2=   D  =< # :    ##  0 2  221; &4  # # >  4#   

(43) < # 2#  #     $     $)   =# ##  #  

(44) A    =0#, -#220# ## : :   # 1A   =0  2 1;  # ### #220    21#   2    !, B  #C  02!,   2    # 1 #  @= 0 2 #  ##< :  :  # . 6.

(45) @@1 #4

(46) $<  2  @#< # @#>####     .   $ B     C B$2)C > # #2 =# 4#  2 1  # $ :  # # # -  # +<-- #: F G< ###= # : 2 1 :   $ 1 2 

(47) 8 =  0 # & #0 : 2 -- # 2 $ # #=22  #:< 1< :  :   $ > #11 2  10  #   # 12 #: F.G 44$>#2##010 #<00< #1#0 & 2 $ > 1 4 # : ##  <  / 2I##=#3,!@5B6K  C< : >  #=  >    #  #  F+GB8CA ;';: :10<2#200=D #. . %.

(48)  3*   !! &  . 4

(49) 567    & 89:  )    . 0   $ # ##  +<-$  B#  #=22 ###C<    ##  2 B  LMC20<<=#

(50) 8 #   2 >  2 21< #  ##0   > 00 4 4,! @5  2E   0  .4  )4 4,!@5<  2   )4

(51)     1:#.? +<-$==0 $<:### 01 2# #<=:0# >2##2##<40$>2  0 : 2## : 2#<  1  # =<#0 ###2#@ ##2# .<-" +<-$:2##= 12 # #:  # #< : 1  # :< :  '  220  =#   1#<  @@ #2  : # ## <  >  :   # @#  0    .-/122#. . K.

(52) E 2## =  =0  @  12  0   $  20  2  #A  # 2B

(53) @ C#2##:  12     2=0   .<-< : #   #    2  2     <  2  =0  0   $  012. . /.

(54)  '

(55)  . 8

(56)  . .<-B+.?C" 6<-$$B).?C 8#. <#< 2#012. .<-" +<-N B$N<8$NC. 8# <#< 2#02. 

(57)  $ 8

(58) $ 

(59) . F6G. F%G. %. # .<- .<-B% ?C" 6<-$B%?C # .<-BK%?C" 6<-$B ?C. 8# <#< 2#02 @1:. F%G. %. .<-BK+?C" 6<-$B+?C .<-" +<-<N2#B$2C. 8# <#< 2#02. .<-B%/?C" +<-$B /?C. 8# <#< 2#0### ##. .<-B% ?C" +<-$B%?C. .<-B%K?C" +<-$B?C. 8# <#< 2#0### ## @D <2#0 =<# :<2#0 #5. .K!. FKG. F/G. % -. F/G. &.K1#-+6. F/G. 96 ,. 0 ( .!(* ; .  # #<  #  2#0    # $     # $  #2  2#=D   $<    0   >  1 2<  = #2<2#  4221   < 1< 2D :  @##212. . .

(60)    !"#$"%&"%' .  @# >    2#      2 #  2  2 #   ##<#: #  12 1 : 2#   # $ B

(61) C<2=2#:6 )/?##20:2=0#$ @# > # 2##@ 22   # @   # $ B$2C< : > #  !($ B(   )*C FG<##= ## 4 ##  @#A  #2##  ##       #< #   ##  #       : 22  # . F G<.  @#  < 40 > #.  #  $ #21<   2@@ 10 # B8 C

(62) #>##0

(63) $ F)G F GB%  +  

(64) C<:>#2####F.G<: @##<>2= 0B(#"2C<2#10 2@@###4#      3* 

(65) *..; <2=:((!* 00 .  . .

(66) 

(67) $2#40002##<12 1$;#21#=2 4 : $. F6G  :  /*@  2  6  / = B=@4=C#$     1 4210 < : 22#  #22##@D==#: #  @0<     #  #$#$#./; //2

(68) $ #24#$2242#$ 2# #+3 #$23

(69) $;<;(<;'<;A #$3

(70) $;<;8F%G.  @  1

(71) $ #  =0  #0  /? # # # :  2# : #   )? # # ##10 4#0##2 %*@<2#+#.<+#  2=11#22#0 20%@245221## )."B5C.% "B5)CB8)C. . ).

(72)  $9 $90! &,56. ,$+56. >>. >&>+>,. >2. +& ' ).!".% !"'%@22  ;B$2C !". . '. . %")+.  ;"B$2C !". . !. . %")+.  ;B$2C !". . '. . %BC.  ;B$2C !". . '. . %.  ; B$C !. . '. . %.  ;3B$C !. . !. . %. 3*  & .  *  ;: (  .. ?   !>7 0:!..; .   2  =# 4#2##< 0 > #  1  # # =  $; )<  # # # 1 )#

(73) ;'####3

(74) $OB.+K@2C<      D  2 4#   

(75) ! = 4# 

(76) $; B .6@2C<

(77) $;( B6/@2C $; ) 

(78) $O 22#   #   # # # 

(79) $;&BC

(80) $;B#:C#2=.  4#  #   2=      2#B& 'C##21#

(81) $ #2122 #21=#

(82) $; &

(83) $;FKG#8 . . . .

(84)  3* + ; @ . .  2## ###= > #     

(85) $ # =  #2#@  20  # # & =0 2##@>#222E1=#  =<21####=# D0022: F+GB8)C<:21 00  #1L< : # @#  10  #0  @<:#=2B8.C.  3* ,0* ;!..; .  @##22#:#2)24 =<   

(86) $; 4 4  =  2 =#  . ..

(87)   1 2  # 2E @@

(88) $; B")    #C 9# =  = #   4  4> # 2## 9# 2  4   # 2## 4#  #   = <  2  #2 #< 2   22 00  

(89) $ #   2  # $< #P#00# =# #1 : = 4# 4#2##  # < 2# 22  F /G<:

(90) ;' #   2=  @#   # . +<-$ . <:=4#2##.#$:= #2#=#2

(91) $9#1:

(92) $:    #  @#  : 2   # 2# # ## # 221  =     2  , &  . $=:00*#$  20  

(93)  2  2  # #2 =00:#$B8$< ($< $< $)< $< $<

(94) $< ($< ($ < $< Q$< ($C<  #2>=:2E##@2## 2#0  1  # $< : 1#    #:  @#  6  )/? &   00>'<##@D:2##=2#0 1#$:#2 .<-F GF G F )G.  # #     8 , >   . 1   #  '< < =# 420   # 2#=<  # >   00 2E    2 1#:##2##@D14# . +.

(95) #  2   #@@  2  22 =#= 9# 2  < 1< 1 2    : = 1 #20

(96) #&4#'>2 #2D0002#<: ##=.  :#21>00 :###@'<#21= 

(97) @)# 2  #2  :  : = 00< #   ;'< 98;' B-)   . + )  'C< M#   .    . 3. 98;'. '##4210

(98) :. F G. 4#211< ###=1#2##0 <1#0#=#2## ##2#2 1'. &

(99) '. '=<D2=. F G. 2#0 0<10 ==#@#1#0 ## <=## :2 #21:. M#. =24=0 #<@#. F .G. #0##  <:==

(100) <= 001#0=# 1##1<:2< #D>##>220 2#. 0 &(A!).*   . . 6.

(101)  / 0   &2#00#20:##  @## #<  20  @## #"

(102) "  &;R< : 2KK6410=2 2#00=22#F +GF 6G.    , - B*    ) *(

(103)    C 22  -2 ) "$2) < 2    / Q@<  #  % #     1 B  %C  # # 1 2  ##2=:# 2### ;<  11 ';3 :5 B K C  :5@ B .C @  2 : 10 1 *(B8 +C<# 21#0 #2  #2:< = 4@#< : #  2##=#=0.  3* 2

(104) ...0> <$=:189!. &.**B)C .  . %.

(105) @  2 # #2##  4@#   4 <   #      #   0   , - # ##  @## #  ###   &J;R B&RC3 1D    2#< #<@###B.CA#2##&B1 0  &RCA  

(106)  B2#110  , -CA   @## # 2 B C   # #< 2   40   , -< 0 21  2 0<411#@##2 @  <#:, -###; 2 9# >  : # =1  

(107)  = 42#110  , -< #  2 4  # -< >   # 22< : #  4<  @## #  1  #<   # : =  #2#  2  !,  20  

(108)   20  

(109)   0   , -< # :  <   #  @## # > 2@  , - 4>  @ #2#  2<   # 1  #  

(110)  >  #2  

(111) F KG9#:5  *12:= !,><@##= !8###20 0   , -<  4 : , - 2## = # @#4 !8>#2#F)/GA#2#:40:5 #  2##  1#  21#   0 #:<  2  <  0 2@@ ## 2#  2#0    =  !8   2 #!,. . K.

(112)  3 0 . !,>###.2);2 F)G<# # 2 2E  +/ Q@  > #  / #  2 #  24# #1A#4# 12 22 #  2  2    5<  #  )  6 1 2   5< 4# % 2  #@#K/2 =2!,2212  : & 2 > 2#   +)%   3 % #  22 #< +   5<    #@)./2#'@ 22 :  #  #@< > 2=  =D :# #  > ##   #:#  1 S# B ##21S* C !,1=#000 <=#2#@2#0#<:2 20 112#B86C0 !,##2#@&F) G<#  # ##=< 00  @## # 2 ##0  !,< 1# 2 B1< @00 1 2<   # #< 2 C< @#D< ## #< # 2#=22 . . /.

(113)  . ' . 

(114) . 

(115) &. !,,N. ;  

(116) 

(117) 

(118) .  8 . ' &. 54. . 54. 8!

(119) .

(120)   . 53.    ''

(121) . . 3* D .(((1(54 .     !, ##  =     0   6 *@ 2 4 # )3 # #  1: ##:=2#0#0=B&

(122) C:< 2@@  #   =  @0  #<:#45##12#  B8 %C F))G 9# = >  21#<   10 2 4 )  .;) ?   10 2  0  K; ?< :< #@@  # ##  0 2:<  > ###0 F). G F).G<==0. 2!,@###<==#0 : 4

(123)  F)+G   # # # F)6G F)%G   =0  ##:2E2>##2:##22 =# 10 ##  # F)KG<   =  1@@#  . .

(124)  @ #1   #    #2  #=0   !,<   4=D > #   2#0  2 0 1"1< 0 1")  0 )")<   # = : 4=D   1")  )") #2  )/?1"1.  3* $ ...1>1&:. 1.A!(@ B**C .  '   #  =< : # 2@@  #2:  0  ==<  1  2#0   # 2 4 ) #@###112##= # #     =0  2 1< : 2I<    =#D  #< = =2E#. . .

(125)  &.

(126)  @ 

(127) .   

(128)    9##2+ #:22##D  20    :;

(129)  # 2##     < @     < 40 #2;=#  #;2:  ( &  2  ## # > 2#  # 2 @## # "  2A   4# # #3 12 1 #0 @D   = < @## #< #: 12: 2:  #< #  # - &4#  2 # : =0  # 23 +? .<-</? +<-B-C<)? +<B-C< ?#B %? .<-" +<-- )? .<-" +-B-C< +? #  $C

(130)  # +  20 # # #0 +% 20 : ==   #1B8C<:>##2##0##.   **  B

(131) ,C3  TB8;

(132) ,CA  0  #     

(133)   F. /G3  

(134) A   0  #.  2 ##=0< 2 / B#2##    0  #

(135)  C3TB8;/C. =###2##B . C. . ).

(136)    

(137)  

(138)  

(139)   # 00 = #2#   2=  # 21  /  : = #=  ;%/U '   4#02===#<= #       * Wizard Genomic DNA purification BC<4>24=##0 2 4#0 =   0     #21 B   ,444 (C<     = #=  V /U'    2 4#  0  ./"µ=1N U'    & 0  ' 2   $    $) # 2 

(140) @.   2# 00 # #2@  . F G F G. . :20

(141) 4#4210 # $ ##  2 #J  #< > # 22  #  2 2   $< : 2= 4#      '<  4#     210  #: B2#=C1B=C  ... A!(,1→ →&1. .. 18B##C. !!

(142) !

(143)

(144) !!!!'!!!

(145) !'. + U'. 1=B##C. !

(146) !''

(147) !

(148)

(149) '''!

(150)

(151) !

(152) '. +/U'. $)8B##C.

(153) !'

(154) ''!!'

(155) !. .)U'. $)B##C. ''

(156) ''!'

(157) 

(158) !. .U'. 88B##C. !!''!

(159) ''!!

(160) !!. .KU'. 8B##C. !'

(161)

(162) '

(163)

(164) '!!'!'

(165) '

(166)

(167) . .%U'. 0  + . !((      * ;   * ;&:    A!(.* ;B333 C . .

(168) . =1#20'2$ $)>./µ // </2  2   2# 2    B). 2C< 

(169) # //  <   0  .µ  #2 @11 /5< ,  # @#= 4 # 00   2   #21D  0 & 0#21:210#2

(170) @.  3... BEC. .. E. A* . $. K.. .4. .

(171) 9:B).C. . . . . .   %. K.. /44. +. /44. 6 . .44. . $). .  . . K.. /44. .K. .44. 6 . /44.  . .. . . 6 . 64. K.. .4. .

(172) 9:B).C. . . . . K.. )/44. .   %. . . )/44. /. . 6 . 4)/44. . . . . . K.. )/44. . ./. )/44. .. 6 . 4)/44. . . . . 6 . .W. . 0 ,.(!((* ;BC7* ;&BC . . .. .

(173)  &4#'>#=11###    

(174) 

(175) 

(176) 

(177) 

(178)   .  #  2#=H  0  '   $ = #2#  #0. 2. 4=0. . =. 0. &. 2102'=##20#  B56"-) ' ')+  7  5C<  1 21 =  #2#  0  #0 B( #%

(179) 5)      $C  400  2#  '    2# 1B

(180) @ C 20#0=  # = 21  220   Q  B-

(181) ' 7 668!8#6"C#2##0 '9%///B$C  . !

(182)   "

(183)   

(184)

(185) 

(186)  "   #

(187) 

(188) 

(189) 

(190) $

(191) % 

(192) &'.  &=01004#)!,># 110025'#:# F))G. 20#2

(193) @+ ... A!(,1→ →&1. .. !B##C.

(194) !

(195) !'

(196) !!

(197) '

(198) !

(199)

(200) !!

(201) '

(202) !. .K.U'. ! B##C. !

(203) '!

(204) 

(205) ''

(206) !!!'!!. .K.U'. !)B##C. ''

(207) !!

(208)

(209) ''

(210)

(211) 

(212) !'!'

(213) '. +.U'. 0 2 .!((.>  1&54 .  . +.

(214) & #  0 > #P 2#3 6.   A 6. 2  #2A//µ

(215) #A  ?A.

(216) 221 = @11 /-  1 ,  @# 1    = 1 .µB>##=0 20=2#2##0C. 2@@>#1@####2 200###>##3  . BEC. .. E. K . .4. . . . . K . )/X. . + . )/X. /. 6 . .4. . . . . K . )/X. . +/. )/X. /. 6 . .4. . . . . 6 . 64. . 0  D   .( !((   

(217)

(218)   ( 1&54  . .  2##@ 2  # 0 #  B8 KC3  22 55&   1  K). 2@ #  2#0 4 !,1 B1 :C     2 5 #    #0    2 =  0<  2 5&  #    0 0### 25#0= 0<2255##0:# . 6.

(219) @B#:2#0:1;:C<  #   4 !,) B 2 4# )C 21  1  .)  2@A  #     !,1 21  1) %2@B#1>#0   2     # # 2#  1  #1=C

(220)   2#= = #2#  0  ' 22#30!,1A 0!,)0!21##2#  # 1    #  ?  0   @ 2 /   +/ 7<  #    = #2#  #   = 11  # 2  @>#3 0!,134@#&,0 0!,)34@,&0 03@#&,0@,&0. . %.

(221) @@ @ 54 F.  !! ) %2@. . 5Ÿ Ÿ⇐ ⇐5 ⇐ ⇐5&.    !!)K).2@   @@ @ 54 &F.  5Ÿ Ÿ⇐ ⇐5 . .   !! .) 2@  -)&

(222) .  3* # ..!>  !)!*54 54 & . . . K.

(223)  ( !)  25&;2@21B&C';,@=< #<

(224) : :# &4#&2=4@0#: #21: # #0 @#3  # #  2  #0   )4    .4A #    22 2  ###=    #D   #0 @#   #D #  # @  2#  #0   # 22  2#3 $  .4  2   #<  -  )4 : ##20=#:002##< 2 #P  #20   2   0 #  &4 1# ##    ' = #  #0 # ###@=21

(225)  #1*<22=3. . )/.

(226)   0    B /;.// C  K%U' 2 .     = 

(227) , 1=1.Y  @0K%U'@0.* B+C  +/U'< 2 =  . Y   "" (

(228)   . Y  &'" $)++ )    . U' 2 . < 2 =  )  Y 3 )Y ()++ 

(229) 93"<)Y()++ 

(230) 93$< .Y, Y

(231) 93 =040K%U' '2053 Y""'$)++4< +Y , </Y0  41+/U'/Y 2#;5 B  Y  "" '

(232) <  Y  "" 8:2 # ) $)++<..Y, /.Y  C210 # 03 ). 3 )/ #  K.U'A )/ #  +/U'A +/ #  6 U'A /16 U' .1###0'9%///2022  #3 /6Y  0  '< /.Y  $ #

(233) (  94

(234) 944  )  1*   . /Y  & B#2  #C. 1##03

(235) 2./U'A0 K/U'2K/#A20+/# /Q7A2#3+/  %Q7 +#'9%///1M###1L  &2@524#, -)K#  #< .##21:B

(236) @%8/C3 2;< %2##, -<.)4#2, -#2   2## # @ < ) #21:  #$<.#21:#-<  ;  . ).

(237)  @!*(( BC.  0G. (... + ;6/;6+;% . 9;@#Z. . K . M:'2@.  . . . . )K. '2@/+;&/6 6.  .  %. '2@/. ;&// . /. .6. 2@/+. ;&/ ). -; <225+/@1, -. ++. , -2@ .;&/6/ . 5. 6.. '2@)/;& ../. -. % . 

(238) $2@/%.;&/ + . $<225.@1, -. K). '2@/+ ;&//./. ). / . , -2@ +;&/6/). 5 . . '2@/+/6;&/.K. K2 . /. 2@ K6.;& /+. -2<225K@1, -. K. 82@/% ;&/ +.. -2 <225.@1, -. )%. '2@/+6 ;&/+K. % . 6. , -2@ 6;&/%/ . 5). .+. '2@/.%6;&/)% . % . +.. & '.K/.2@) ; &/%%6. 6 . $2@/ );&/.K+. $2)<225 @1, -. %). '2@ 6;/66. . K%. , -2@ %;&)). 5 . )/. 

(239) 2@.);&/6 . <2;2##. )K. &'2@/%K;&/))6. - %<225@1;. ) %. 2@ .++;& / 6. -2<225K@1, -. ))6. , -2@ K;&/K/. 5.. ) +. '8 2@6/;&/6/. <2;2##<[%//Q@1 , -. )... $(&2@.+;&/+.K. ;2##</@1;. )+ . '$2@/ +;&/) . $<225 @1, -. . Q@@1, -. ).

(240) @!*(( BC.  0G. (... )6). '2@ ).;&/66). . )% . , -2@./;&/K. 5+. )K. '2@/K%;&/./+. 2 . //. , -2@.;&/6/%. 56. /K. '%2@/% /;&/))%. - .<225 @1, -. %. 2@)).;& / . -2<225K@1, -. 6. , -2@. ;&/6/K. 5%. )+. '2@/.;&/.K.. / . .. '2@. /;&/K/K. 2+. . . &)2@) ;&/6. 2;2##. +). '2@/K6K;&/.+%. /2 . 6..  %2@ 6 +;&.%%. <@L-2, -. %.. $(&2@6+);& ./.  ;2##</ @1;. 0 $ !((

(241) @  . . < < -2 , Q@@1, SHOX CSF2RA IL3RA ASMT SRYUTY SMCY OA1 PPEF1 AR PDCD8 L1CAM SYBL1 PAR2. ; X. . 3*  ' .  ( .. .)  ,  7    * !!. B )C7  ;9 B((!C7H9B0!C . . . )).

(242)   2     #< =  4#  2  <  #:   1 &4@0#1=4##2=   1  > # 1 #   1 5 & 0  =< : =  / B0 0C   B##0  0C < = 1 # @#  22   = =2=2#  # =< #2    #< #  = 22=200#= #  . *      &4# ## > # #  4#  #1L  4 # =  0  23 T8;

(243) ,< 

(244)   T8;/<    2##@2204#!,B1"1<1")< )")C 4 # 22 4  7 #< 

(245) ;   (1 # 22

(246) A2=T8;

(247) ,TB8; /C > # ## 22  #  2 Q#*:;R#  ;R:M#>##@#1=D22\//. . . ).

(248)  +.  @. .  

(249) 

(250) 

(251) +,

(252) 

(253) 

(254) 

(255) ,-  &4#   $    $) > #  # + 20<#4##2 #%&4###<1<==#  2#0  # $   # + 20< 4#  ' $$):#K  20 # 2#= # # 

(256) @ K  #   20 : #@ <    4# # : =0  2#0  @# B  # <     @C<    # #  2 #  == =02#0#$B .<-" +<-NA .<-C '

(257)  . . $. $). 45,X. N. N. 45,X. N. N. 45,X. N. N. 45,X. N. N. 46,Xi(Xq). N. N. 45,X/46,X+mar 20%. N. N. 45,X/46,X+mar 14%. N. N. 45,X/46,X+mar. N. N. 45,X/46,XY 70%. N. N. 45,X/46,XY 68%. N. N. 45,X/46,XY 32%. N. N. 45,X/46,XY 40%. N. N. 45,X/46,XY 35%. N. N. )..

(258) '

(259)  . $. $). 45,X/46,XY. N. N. 45,X/46,X(Yidic) 21%. N. N. 45,X/46,XY/46,X(Yidic)12%. N. N. 45,X/46,X (Yidic) 33%. N. N. 45,X/46 X (Yidic) 16%. N. N. 45,X/46,XY/47,X(idicY) 72%. N. N. 0 #(!)   ;;& .    #  2 .<-   #  2 +<-B-C< > #     ## ##  8 ,<  # #21:#$B$C #1 2#01#$#2  #2 .<-3##2#=#2 :2$+?1#00A##2#= #22$$.?00A ##2#=2/%?00 2$4?00A#2 +<-B-C #>#2#=#2$ .?00. #>#=02#0$B8C< #>2#04#1<# #=00##20 . . )+.

(260) &+,2D? ? "/. - %//@2.   .   &? ? "/. //)@2. ;&. .   3*   3* 1  ! *       *. ;BC*;&BC . . )6.

(261) .  !)  &4#  & > #  #  #  20  2  # : #= 0  @   #-$:==#1<#2 =#, -&4#># &:=0 2#02 2, - #<4#:=00# B

(262) @/C:0#2, - > ##  @## #<  # 4 & # # =  0#12000<:>##2##   B  .  C  # @#  #  1 2 20  

(263)    #2#    

(264) A   110  8  

(265) , BT8;

(266) ,C< = 4 >  # @#  220 1  <#=#1B8C % 0*  B ##2C .   . . 4H. I   B 394C.  . .<-" +<--2;. . ; 6. /. +<--2;" +<-B-C" 6-B-CB-C. . ; .. /6. +<-B-C. .  . K. +<-B-C" +<-B-C. . . K. +<-B-C" .<-. . ;/. /6. .<-" +<-N ?. . / .  . .<-" +<-<N)6?. . ; ). /6. .<-" +<-<N ?. . ;/+. )K. .<-" +<-B$C))?. . ;/+.  . )%.

(267)   . 4H. I   B 394C.  . .<-" +<-B$C ?. . ;/. %. .<-" +<-B$C+?. . ; .. /.. .<-" +<-B$C/?. . ; . ). .<- ?" +<-$ ?" 6<-$$ ?" +<-<  'B$C6 ?. . ;6. /.. +<-B-C. . ; .  . .<-" +<-B-C. . ; K. ;/6. .<-" +<-. . ;/K. +. .<-" +<-B-C. . . /. 0  '  ! 

(268) @ :    ?   *  * 4HB..:C7!) )  I   B49 3C    :  **  )   ( 54 .     ##  20 00<  > # 2##@ 22 4@0 ##  <   =0 >  2##@  @#  =  

(269) < ##   #    > # 1 2  !,< # ##= 4##0   22 ##0   #   , -< : # #    #  2  2  4 

(270)  > 2  K<   # ##   =  = 2   20< 2#  . := ;/6)K< 2  @# =T8;

(271) ,###= #=2#=B C< : #  #1 :  # 1  >    2=#  @#  #      220 1 ### , -#.   4#  &   . # #21:< 2  % 2   , -< : #  2 #=22@  2<    ##@D    2=#B)/?C #1 <)< .#2 . )K.

(272) #2 : #  #    .   # 2E #1=  .<-/ ?" +<-$ ?" 6<-$$ ?" +<-<  ' B$C6 ?   / /% /+ / /.  %  ;  ;   2 . -.  .  2     8 ;       .  ' .  . -. -. 2. -. 2. -. . $.  2. -. .  '. $.   $. Q.   @  .4  ,. 5    5    5  )  5    5  .  5  +  5  6  5     % '  8 2;     2  .  &)    $2 

(273)  )   $. //.  3*    **  , * .. . .

(274) @ : . ! ..   * ! H6;   * 4H: !    * H6;   * 

(275) : !   !  *   .. ;: ! ..  !  *   .. H:  !) !   * A   :(!..; .  +<-B-C" +<-B-C  / /% /+ / /. Q@   .  4  ,. 5  5   5    5 )  5    5 .  5 +   5 6     2; ' %  8 2      &  )  -2

(276)  -2   -2  -2  -     ; 8 -  .    '    %  ; ;   2 . //.  3*  &  **  , * .. . .

(277) @ : . ! ..  !  * ! H  @ * ! HA !      (  ! .. H    .  . /.

(278) .<-" +<-B$C/? /% /6 /+ /. / /) / /. - %  ;   ;   2  . $    '$ -2   -2   -2 . -2    -  8  ;   -  .   ' $ .  Q@  . 4 ,. 5    5    5  )  5    5  .  5  +  5  6  5    % '  8 2;    2  .  &)    $2 

(279)  )  $. //. . 3*  +  **  , * .. . .

Riferimenti

Documenti correlati

2) di più se la demolizione avviene al di fuori della cellula 2) di più se la demolizione avviene al di fuori della cellula 3) le stesse, indipendentemente dal sito di demolizione

Il Dottorato di Ricerca in Medicina e Clinica e Molecolare rappresenta un corso di alta formazione su tematiche di ricerca di ampio respiro ed elevato impatto sociale

AMMISSIONE AI CORSI DI LAUREA MAGISTRALE A CICLO UNICO IN MEDICINA E CHIRURGIA (CLASSE LM-41). ODONTOIATRIA E PROTESI DENTARIA (CLASSE LM-46)

La nuova delezione c.1390-1393 che causa una sequenza 13 aminoacidi più lunga nel sito di legame con la trombina, fu riscontrata in un paziente asintomatico (paziente 13) in cui

- biofilm: è una matrice composta da esopolisaccaridi (Pel e Psl), proteine, DNA/RNA extracellulare, che svolge una funzione protettiva nei confronti di fattori ambientali

La survivina gioca un ruolo chiave tra la regolazione dell’apoptosi ed il controllo della proliferazione cellulare. Come le altre IAPs ritrovate nelle cellule

compute the total cost function, the average cost function and the marginal cost

In ragione di quanto così previsto, è stato introdotto un duplice livello dichiarativo, imperniato sulle dichiarazioni individuali delle controllate (e della