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Medidas discriminatorias como la segregacin racial, esterilizacin de individuos con retraso mental, restriccin de entrada a determinados emigrantes& Mientras los polticos eran los responsables de la implantacin de estas medidas, algunos cientficos apoyaron y justificaron  cientficamente con entusiasmo estas medidas. El momento histrico en el que las leyes eugensicas alcanzan su punto ms aberrante fue 1933 en la Alemania nazi. A a la esterilizacin obligatoria de los que padecan retraso mental o de enfermos afectados como por ejemplo de Corea de Huntington, sigui la eliminacin de estos individuos as como de los que padecan malformaciones congnitas. Actualmente el trmino  consejo gentico es un trmino muy extendido tanto en los profesionales de la medicina como en los pacientes y sus familiares. Unos y otros utilizan este trmino de distinta manera, y as mientras unos le dan un papel de apoyo de tipo psicoteraputico, otros lo ven como la aplicacin de tests diagnsticos de una enfermedad hereditaria o como un complejo proceso matemtico del clculo de riesgo. Todos estos puntos de vista son ciertos pero ninguno define por s mismo claramente el proceso del consejo gentico.xnx 3uf 3fff 3 fff  H D 0޽h ? ̙33___PPT10i.E+D=' d= @B + 0   ` ( dR  t  0`z  :EL CONSEJO GENTICO  Es el proceso por el cual los pacientes y sus familiares con riesgo de una enfermedad que puede ser hereditaria, son advertidos de las consecuencias de la misma, de la probabilidad de desarrollarla o transmitirla y de las vas por la que puede ser prevenida, evitada o mejorada . Peter Harper en su libro Practical Genetic Counselling  Un proceso educacional que busca ayudar a los individuos afectos y/o a riesgo, en el entendimiento de la naturaleza del desorden gentico, su transmisin y las opciones que se abren en el asesoramiento y el planning familiar . Kelly en Clinical Genetics and Genetic Counselling  El procedimiento destinado a informar a una persona sobre las posibles consecuencias de los resultados de un anlisis gentico, sus ventajas y sus riesgos y, en su caso asesorarla en relacin con las posibles alternativas derivadas del resultado . Carmen Ayuso, Comit Nacional de ticaPxx x33f333333f 33*3333f'33G     H  0޽h ? ̙33y___PPT10Y+D=' d= @B +o0 p&( w   0e40  *EL CONSEJO GENTICO Estas definiciones convergen tres aspectos: - diagnstico - estimacin del riesgo - apoyo en la prevencin En definitiva lo que el CONSEJO GENTICO debera transmitir a las familias afectadas por una enfermedad de origen gentico es la informacin sobre: 1) las consecuencias de la enfermedad 2) la probabilidad de desarrollarla 3) la probabilidad de transmitirla 4) las vas existentes para: prevenir, evitar y mejorar la enfermedad $x'xx3fflf'f$  f'f!f'fXf fZ iH  0޽h ? ̙33y___PPT10Y+D=' R= @B +P0 wo( w V  0e  0RBOL GENEALGICO El rbol genealgico proporciona un registro no ambiguo y permanente de la informacin gentica de la familia. La utilizacin de smbolos claros y consistentes permite establecer la informacin gentica de manera mucho ms clara que con interminables listas de familiares. pxx 3ff0 P  c (A" \1}`lP  c (7A 2 0   s *eX  b(Varn, Hembra (no afectos)) 2) 33   s *eX  JSexo desconocido 2 33   s *de@ M  aVarn, Hembra afectos0 2 3333  s *#e @ P  Z3 varones no afectos* 2 33  s *$(e :  ^Fallecido y afecto0 2 3333  s *4-ec @   cExaminado personalmente0 2 3333  s *1e @  bIndividuo sin descendencia, 2 33  s *6e3 @  cMatrimonio consanguneo0 2 3333  s *=eS@@  aDescendiente no emparentado* 2 33  s *@@e3 @Aborto 2 33  s *`Dep  AGemelos 2 33  s *GeP p  [Gemelos monocigticos* 2 33  s *Ke M  KHeterocigoto (AR) 2 33  s *Be u  THeterocigoto (Ligado al X) 2 33  s *Te  BProbando 2  33H  0޽h ? ̙33y___PPT10Y+D=' R= @B ++0 B:(    0|Ye,V ~HERENCIA MENDELIANA Una de la preguntas que se nos plantea a la hora de realizar el consejo gentico es si la enfermedad a la que nos enfrentamos sigue un patrn de herencia mendeliana. Es posible que la enfermedad no sea de origen gentico por lo que podremos excluir el riesgo de recurrencia de la misma. La herencia mendeliana se establece frecuentemente por la combinacin del diagnstico clnico y el rbol genealgico. x3ff3ff3fyf3f  J  S "A 3@ J  S "A 4 P H  0޽h ? ̙33___PPT10i.E,lt+D=' R= @B +U0 |t0(    0TY  zP Enfermedades monognicas Son el resultado de cambios muy especficos en el genoma del individuo enfermo. Se transmiten de generacin en generacin siguiendo un patrn de herencia mendeliano: autosmico dominante (AD) autosmico recesivo (AR) recesivo ligado al cromosoma X (LX) Son muy numerosas pero poco frecuentes.SxxYxZxx*x 3 334fff9ffffffffff)ffP    4 +B  s *޽h ? ̙33y___PPT10Y+D=' R= @B +Y 0 p h  (    0se9 h La enfermedad AUTOSMICA DOMINANTE puede definirse como aquella que se expresa en el portador de un solo alelo mutado (heterocigoto). El riesgo para los descendientes de los afectos es del 50% sin influencia del sexo. En ocasiones las enfermedades que se transmiten de esta manera como la enfermedad de Steinert, las cosas se complican ya que existen dentro de una misma familia individuos que son asintomticos, individuos escasamente afectados e individuos gravemente afectados: variabilidad en la expresin. Distrofia miotnica tipo 1: causada por repeticiones inestables del triplete CTG en la regin 3 no traducida del gen DMPK (Dystrofia miotonica protein kinasa) localizado en 19q13. Tamaos de > 50 CTG aparece la patologa. Pacientes con fenotipo benigno: 50  150 CTG Pacientes con fenotipo clsico: 150  1000 CTG Pacientes con forma congnita: >2000 CTG x{xhxxf3fff33!2ff%fff%fOffff fff4    i           @`H  0޽h ? ̙33___PPT10i.Ep* +D=' R= @B + 0  =(  V  S .A neuro 1M   <eV <  P  C (Aneuro10P m   0Dep s gHerencia autosmica dominante. 2fK  0  T  S ,A neuro3  @ 0Le-  >    <0e *  >    <m *  >  Z  c 2AH neuro5C 2    0m~  < 2     0m G @ c Herencia autosmica recesiva*fH   0 m0  lRECESIVO Se dice de un alelo o de una mutacin que solo influencia el fenotipo si est en estado homocigoto` cxX    s *m`  F Progenitores 2  3   s *m0 T Gametos. 2 33 3  s *m   X Hijos0 2 33 3  s *X%m P  SAfectos0 23 3  s *)m 0   @Normal 23R  s * p  s *D.mP   V Alelo mutado. 2 3 3  s *2m Pd  QPortadores no afectos (23  0T2/  g  < 2  h  Bfv޽h @ ?"` ̙33y___PPT10Y+D=' R= @B + 0    (  Z  0p:mPP DISTROFIAS DE CINTURAS RECESIVAS (Limb Girdle Muscular Dystrophies Type 2) Localizacin Enfermedad Gen Protena gnica 15q15.1-q21.1 LGMD2A CAPN3 calpana 3 2p13 LGMD2B DYSF disferlina 13q12 LGMD2C SGCG g-sarcoglicano 17q12-q21.33 LGMD2D SGCA a-sarcoglicano 4q12 LGMD2E SGCB b-sarcoglicano 5q33-q34 LGMD2F SGCD d-sarcoglicano 17q11-q12 LGMD2G TCAP telethonina 9q31-q34.1 LGMD2H TRIM32 tripartite motif 19q13.3 LGMD2I FKRP fukutin related protein 2q31 LGMD2J TTN titina 9q34 LGMD2K POMT1 protein0-manosil transferasa 1 9q31-q33 LGMD2L FCMD fukutina 11p13-p12 LGMD2M ? ? 14q24.3 LGMD2N POMT2 protein0-manosil transferasa 2 "3333333333333533ffDfffffff ff)ff)ff(ffff.ffff ff)fffffffffffp# \  $  !   #':B  s *޽h ? ̙33y___PPT10Y+D=' R= @B +?0 VN(    0$vmfp  NfLa enfermedad RECESIVA LIGADA AL CROMOSOMA X es aquella en la que solo los individuos varones estarn afectados. La transmisin varn a varn nunca ocurre ya que un hombre no transmite su cromosoma X a su hijo (ej distrofia muscular de Duchenne). Por el contrario todas las hijas de un varn enfermo sern obligatoriamente portadoras (ej distrofia muscular de Becker). Los varones sanos nunca transmiten la enfermedad a sus descendientes sean del sexo que sean. El riesgo de una mujer portadora de tener hijos varones afectos ser de 1 de cada 2, y la mitad de las hijas sern a su vez portadoras.Psxxf3;ft    [    < H  0޽h ? ̙33___PPT10i.E0O+D=' R= @B + 0   l (    <`m* >    <$mGzA >    <mv  >  Z  c 2AH \neuro7@ `   <Ȑm& <    <Дm: <  V  S .A  neuro20   M   <Pmj  F2    0mA ! 4 Herencia recesiva ligada al cromosoma X85.ff   s *ءm' F Progenitores 2  3   s *\mj ` T Gametos. 2 33 3   s *ğm `Z  X Hijos0 2 33 3  s *m 0t  Y Hijo afecto2 (2 3 3  s *m ` t  T Hija normal, (2 3  s *\m t  JHija portadora (23  s *m t  Y Hijo normal2 (2 3 3  s *tm  5  V Alelo mutado. 2 33R  s *P ` R  s *P @ h  Bfv޽h @ ?"` ̙33y___PPT10Y+D=' R= @B +;0 RJ (  R  0m9Y  Existe por ltimo un tipo de herencia mucho menos frecuente, tambin de tipo mendeliano, que denominamos HERENCIA MITOCONDRIAL. La mitocondria es el componente celular adems del ncleo que contiene DNA. Su genoma es pequeo y circular y presenta mutaciones que son responsables de diferentes enfermedades hereditarias (ej miopatas mitocondriales). El DNA mitocondrial es exclusivamente de origen materno. Ambos sexos pueden estar afectados, pero no habr transmisin de los varones a sus hijos hx|xif3ffZE       P  c (AW \6T pH  0޽h ? ̙33___PPT10i.E p,++D=' R= @B +0 "0(    0m@   Enfermedades monognicas Son el resultado de cambios muy especficos en el genoma del individuo enfermo. Se transmiten de generacin en generacin siguiendo un patrn de herencia mendeliano (AR, AD, LX). Son muy numerosas pero poco frecuentes.Sxxgxx*x 3 334ffSffEffB  s *޽h ? ̙33y___PPT10Y+D=' R= @B + 0 1)@( w   0s ( )DIAGNSTICO Un diagnstico claro es la base esencial para un consejo gentico apropiado. Por tanto la primera tarea del consejo gentico es el establecimiento del diagnstico exacto combinando la tres reas de conocimiento: clnica + anatomo-patologa + molecular. En la actualidad son numerosas las enfermedades hereditarias en las que puede realizarse el anlisis del gen responsable: DIAGNSTICO GENOTPICO O DIAGNSTICO MOLECULAR Este tipo de diagnstico permite: 1) analizar la causa primera de la enfermedad, 2) validar el diagnstico en un individuo sintomtico, 3) efectuar el consejo gentico en la familia mediante: - la deteccin de los individuos portadores y - el diagnstico prenatal en los embarazos de riesgo. No obstante, aunque en el diagnstico de algunas enfermedades neuromusculares el anlisis del GEN es el test primario, en otras es necesario realizar estudios inmunohistoqumicos de protenas especficas del msculo previamente al anlisis del gen. x 3fffff f~f.3.fH    G H  0޽h ? ̙33y___PPT10Y+D=' R= @B +3 0 ZRPM(  L4 L # Y L 6|sA ICromosoma, DNA, Gen!4 L # 8  L 6m`  2Adaptado de Understanding Gene Testing , NIH, 1995(3' ,  qL  L#  :N (F L p{`8N (F L (F  L BCDEF XEE  &/7@KT_ju Xj_TK@7/' uj_TK@7 /&'/ 7@KT_jX@` ^ d  L B C DEF XEEw | ! 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T B{s?9 ^PROTEINA& 0U N     T   f  T 6?    T B s?#  ) YRNA&0U fB  T 64?  fB  T 64?  T B$s?p ,$D 0 u Transcripcin*0U   T B4s?i ~,$D 0 r Traduccin* 0U  B T 6?G,$D0B T 6?9 9 M,$D0h T Bfv޽h @ ?"` 33y___PPT10Y+D=' R= @B +0 pE( w    00sp@T  PRINCIPALES PARMETROS PARA LA ELECCIN DE ESTRATEGIAS DIAGNSTICAS LA ENFERMEDAD EL GEN LA MUTACIN LOS TRANSCRITOS DE RNA LA PROTENAFZD33333f 33f 33f-33f H  0޽h ? ̙33y___PPT10Y+D=' R= @B +0 &(   ~  0s   PRINCIPALES PARMETROS PARA LA ELECCIN DE ESTRATEGIAS DIAGNSTICAS LA ENFERMEDAD: mutaciones (cambios patolgicos) en genes muy diferentes pueden originar un mismo cuadro clnico (heterogeneidad gentica). UNA ENFERMEDAD varios genes posibles - Nmero de posibles genes para una misma presentacin clnica. 6HxE333 33dffff33Wffffff(L  H  0޽h ? ̙33y___PPT10Y+D=' R= @B +u 0   2 (    0sn DISTROFIAS DE CINTURAS Localizacin Enfermedad Gen Protena gnica 5q31 LGMD1A MYOT miotilina 1q11-q21 LMDD1B LMNA lamina A/C 3p25 LGMD1C CAV3 caveolina 3 7q LGMD1D ? ? 6q23 LGMD1E ? ? 7q32 LGMD1F ? ? 4q21 LGMD1G ? ? 15q15.1-q21.1 LGMD2A CAPN3 calpana 3 2p13 LGMD2B DYSF disferlina 13q12 LGMD2C SGCG g-sarcoglicano 17q12-q21.33 LGMD2D SGCA a-sarcoglicano 4q12 LGMD2E SGCB b-sarcoglicano 5q33-q34 LGMD2F SGCD d-sarcoglicano 17q11-q12 LGMD2G TCAP telethonina 9q31-q34.1 LGMD2H TRIM32 tripartite motif 19q13.3 LGMD2I FKRP fukutin related protein 2q31 LGMD2J TTN titina 9q34 LGMD2K POMT1 proteinO-manosil transferasa 1 9q31-q33 LGMD2L FCMD fukutina 11p13-p12 LGMD2M ? ? 14q24.3 LGMD2N POMT2 proteinO-manosil transferasa 2 w33633ff!ff ff&fFfffDfffffff ff)ff*ff)ffff.ffff3fff ffffffpg C   $  ! !  '2B  s *޽h ? ̙33y___PPT10Y+D=' R= @B + 0   L (    0z ~PRINCIPALES PARMETROS PARA LA ELECCIN DE ESTRATEGIAS DIAGNSTICAS EL GEN: enfermedades clnicamente muy diferentes pueden provenir de mutaciones en un mismo gen (heterogeneidad fenotpica o heterogenidad clnica). VARIAS ENFERMEDADES un mismo gen ! Nmero y naturaleza de los fenotipos diferentes que pueden derivarse de mutaciones en un mismo gen. Ej: Mutaciones en el gen de la disferlina (gen DYSF). 1) Distrofia Muscular de Cinturas tipo 2B (LGMD2B): afectacin proximal 2) Miopata de Miyoshi (MM): afectacin distal posterior 3) Miopata Distal Anterior (DAT): inicio en el msculo tibial anterior ! Estructura del gen: nmero de exones, longitud de la secuencia genmica. Vjx9I-xxC3333Zfffffffff3fffff+f !-f!;f!%fff3Jff      M)< N H  0޽h ? ̙33y___PPT10Y+D=' R= @B +0 (  T  0zf*,H PRINCIPALES PARMETROS PARA LA ELECCIN DE ESTRATEGIAS DIAGNSTICAS LA MUTACIN: - espectro de la mutaciones ya descritas en la literatura - distribucin de las mutaciones en el gen -  zonas clientes de mutaciones - recurrencia - efecto fundador - mutaciones  privadas (propias de cada familia) Tipos de mutacin: 1. Mutaciones puntuales 2. Deleciones 3. Duplicaciones 4. Inserciones 5. Inversiones 6. Genes de fusin 7. Tripletes inestables LOS TRANSCRITOS DE RNA Y LA PROTENA: la expresin de ambos en los diferentes tejidos y accesibilidad de los mismos. DxC33 33f3333f%33Sf3     H  0޽h ? ̙33___PPT10i.Exi+D=' R= @B + 0 E = (  x  0.z  2) PCR Cuantitativa, tcnica de Light Cycler para deteccin de: - duplicaciones en varones enfermos - deleciones y duplicaciones en mujeres portadoras,33f,'? 'H  06z`' n 1) PCR Mltiple: deteccin de deleciones en los varones enfermos: promotores cerebral y muscular, 25 exones<o33\f E  0p=z8@ + TCNICAS PARA EL DIAGNSTICO DE DMD/BMD:,3'33  0QzCTw vz3) Multiplex Ligation-dependent Probe Amplification (MLPA): deteccin de deleciones y duplicaciones en los 79 exones que componen el gen. 4) Secuenciacin directa del RNA: deteccin de mutaciones puntuales. Posteriormente se confirma mediante secuenciacin del fragmento correspondiente de DNA genmico. 5) Anlisis indirecto: haplotipos con microsatlites en el locus DMD. zg330g33g33Pgf!g33gff33f3f<                                                  'V  0vvv޽h ?"` ̙33y___PPT10Y+D=' = @B + 0 .(    0_zY EL CONSEJO GENTICO EN UN CONTEXTO PRENATAL DIAGNSTICO PRENATAL El diagnstico prenatal se realiza cuando existe un riesgo a priori de que el feto est afectado. Se analiza el DNA fetal extrado preferentemente de vellosidades coriales que se obtienen mediante biopsia corinica en la semana 11  12 de gestacin. El anlisis del DNA de ambos progenitores es siempre requerido para excluir contaminacin materna en la muestra fetal. DIAGNSTICO PREIMPLANTATORIO Es una alternativa al diagnstico prenatal clsico. El diagnstico preimplantatorio permite proceder a la transferencia selectiva de embriones desprovistos de la mutacin. Examina los embriones creados por fecundacin in vitro (FIV), para implantar solamente los embriones que no estn afectados. .Bxyxxx3xx,!33!=ff5f33ffIfZ  0    I H  0޽h ? ̙33___PPT10i.E BW2+D=' = @B +D0 kc(    <gz:   P  c (A \5P   s *}z })Posible DMB Distrofia Muscular de Becker 8* ffH  0޽h ? ̙33y___PPT10Y+D=' = @B ++0 RJ(  P  c (A  7P   6ȅzD- TPosible DMB LGMD2I Distrofia de cinturas<+ f ff8  6z1 Pj BGen FKRP exn 4 (19q13) c.826C>A p.Leu276Ile tCf/fH  0޽h ? ̙33y___PPT10Y+D=' = @B +]0 |(  L  S $AP6  s *=P  4 SERVICIO DE GENTICA M Baiget DISTROFIAS MUSCULARES Pia Gallano Lidia Sedano Lidia Gonzlez-Quereda Jons Juan M Jos Rodrguez  "# fffff# 7B  s *޽h ? ̙33y___PPT10Y+D=' = @B +@0 P8(  Pd P c $X    P s *+X @   " H P 0޽h ? ̙33_ A0   X (  Xd X c $X     X s *@6X @   %DOGMA CENTRAL: de la Biologa Molecular que consiste en el flujo de informacin que fluye desde la contenida en el ADN del ncleo de las clulas en forma de cdigo (nucletidos) hasta su traduccin en forma de aa que darn lugar a las diferentes protenas. - El ARN es el intermediario en este flujo de informacin que tiene un nico sentido. - Tanto el ADN, ARN y prot. Son largos polmeros, de secuencia lineal de unidades de repeticin. Como veremos poco a poco, la informacin gentica est contenida en el ADN de los crom. del ncleo clar, pero la sntesis de prot tiene lugar en el citoplasma. - El RNA se sintetiza a partir de un ADN molde a travs de un proceso llamado TRANSCRIPCION. Este RNA, que lleva la informacin codificada en una forma llamada RNAm, es transportado del ncleo al citoplasma, donde la secuencia es decodificada o TRADUCIDA para determinar la secuencia de aa de la protena que se va a sintetizar. Este proceso de traduccin ocurre en los ribosomas, que son unos orgnulos citopalsmticos involucrados en la sntesis de protenas.&& :                $             , H X 0޽h ? ̙33rPm1j<A h. 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Barcelona.-՜.+,0(    Presentación en pantalla SANT PAUp' $Times New RomanArialVerdanaSymbol宋体Diseño predeterminadoDiapositiva 1Diapositiva 2Diapositiva 3Diapositiva 4Diapositiva 5Diapositiva 6Diapositiva 7Diapositiva 8Diapositiva 9Diapositiva 10Diapositiva 11Diapositiva 12Diapositiva 13Diapositiva 14Diapositiva 15Diapositiva 16Diapositiva 17Diapositiva 18Diapositiva 19Diapositiva 20Diapositiva 21Diapositiva 22Diapositiva 23Diapositiva 24Diapositiva 25Diapositiva 26Diapositiva 27Diapositiva 28Diapositiva 29Diapositiva 30 Fuentes usadasPlantilla de diseñoTítulos de diapositivaRoot EntrydO)^@Pictures@; Current User2SummaryInformation(yX)_㣵usuariusuari  !"#$%&'()*+,-./0123456789:;<=>?@ABCDEFGHIJKLMNOPQRSTUVWXYZ[\]^_`abcdefghijklmnopqrstuvwxyz{|}~      !"#$%&'()*+,-./0123456789:;<=>?@ABCDEFGHIJKLMNOPQRSTUVWXYZ[\]^_`abcdefghijklmnopqrstuvwxyz{|}~      !"#$%&'()*+,-./0123456789:;<=>?@ABCDEFGHIJKLMNOPQRSTUVWXYZ[\]^_`abcdefghijklmnopqrstuvwxyz{|}~      !"#$%&'()*+,-./0123456789:;<=>?@ABCDEFGHIJKLMNOPQRSTUVWXYZ[\]^_`abcdefghijklmnopqrstuvwxyz{|}~      !"#$%&'()*+,-./0123456789:;<=>?@ABCDEFGHIJKLMNOPQRSTUVWXYZ[\]^_`abcdefghijklmnopqrstuvwxyz{|}~      !"#$%&'()*+,-./0123456789:;<=>?@ABCDEFGHIJKLMNOPQRSTUVWXYZ[\]^_`abcdefghijklmnopqrstuvwxyz{|}~      !"#$%&'()*+,-./0123456789:;<=>?@ABCDEFGHIJKLMNOPQRSTUVWXYZ[\]^_`abcdefghijklmnopqrstuvwxyz{|}~      !"#$%&'()*+,-./0123456789:;<=>?@ABCDEFGHIJKLMNOPQRSTUVWXYZ[\]^_`abcdefghijklmnopqrstuvwxyz{|}~      !"#$%&'()*+,-./0123456789:;<=>?@ABCDEFGHIJKLMNOPQRSTUVWXYZ[\]^_`abcdefghijklmnopqrstuvwxz{|}~Root EntrydO)Pictures@; Current UserSummaryInformation(yX)PowerPoint Document(ǵDocumentSummaryInformation8