The  Chromosomal  Basis  of  Inheritance  

Chapter  15  

Loca%ng  Genes  on  Chromosomes  

More  on  Chromosomes  

•  Mendelian  inheritance  has  its  physical  basis  in  the  behavior  of  chromosomes  

– Several  researchers  proposed  in  the  early  1900s  that  genes  are  located  on  chromosomes  

 •  The  behavior  of  chromosomes  during  meiosis  was  said  to  account  for  Mendel’s  laws  of  segregaAon  and  independent  assortment  

 The  Chromosome  Theory  of  Inheritance  states  that  Mendelian  genes  have  specific  loci  on  

chromosomes,  and  that  it  is  chromosomes  that  segregate  and  assort  independently.    

 It  is  important  to  connect  physical  movement  of  chromosomes  in  meiosis  to  Mendel’s  laws  of  

inheritance.    

Thomas  Hunt  Morgan  provided  convincing  evidence  that  chromosomes  are  the  locaAon  of  

Mendel’s  heritable  factors.    

– Morgan  worked  with  fruit  flies  because    •  Breed  at  a  high  rate    

–  A  new  generaAon  can  be  bred  every  two  weeks  •  Possess  only  four  pairs  of  chromosomes  

–  3  autosomes  and  1  sex  chromosome    

•  Morgan  first  observed  and  noted  wild  type,  or  normal,  phenotypes  that  were  common  in  the  fly  populaAons  – Traits  alternaAve  to  the  wild  type  are  called  mutant  phenotypes  

•  In  one  experiment,  Morgan  mated  male  flies  with  white  eyes  (mutant)  with  female  flies  with  red  eyes  (wild  type)  

 

– The  F1  generaAon  all  had  red  eyes  

– The  F2  generaAon  showed  the  3:1  red  :  white  eye  raAo,  but  only  males  had  white  eyes  

 

• White-­‐eye  mutant  allele  must  be  located  on  the  X  chromosome  

•  Which  one  of  Mendel’s  laws  relates  to  the  inheritance  of  alleles  for  a  single  character?  – The  law  segregaAon:  the  two  alleles  in  a  pair  segregate  into  different  gametes  during  gamete  formaAon.  

 

•  Which  law  relates  to  the  inheritance  of  alleles  for  two  characters  in  a  dihybrid  cross?    – The  law  of  independent  assortment:  each  pair  of  alleles  segregates  independently  of  each  other  pair  during  gamete  formaAon  

Morgan’s  Findings  •  Transmission  of  the  X  chromosome  in  fruit  flies  correlates  with  inheritance  of  the  eye-­‐color  trait  – 1st  solid  evidence  indicaAng  that  a  specific  gene  is  associated  with  a  specific  chromosome  

•  Linked  genes  tend  to  be  inherited  together  because  they  are  located  near  each  other  on  the  same  chromosome.  

•  Sex-­‐linked  genes  

 

The  Chromosomal  Basis  of  Sex  •  An  organism’s  sex  is  an  inherited  phenotypic  character  determined  by  the  presence  or  absence  of  certain  chromosomes  

 

•  In  humans  and  other  mammals  there  are  two  types  of  sex  chromosomes    –  X  and  Y    –  XX  =  Female  –  XY  =  Male  

 

•  Different  systems  of  sex  determinaAon  are  found  in  other  organisms  

 

Anatomical  Signs  of  Sex  

•  Gonads  are  generic  unAl  embryo  is  about  2  months  old  –  developing  into  ovaries  or  testes  depending  on  the  presence  of  the  Y  chromosome.    

•  SRY  gene  

– A  gene  located  on  either  sex  chromosome  is  called  a  sex-­‐linked  gene.  

•  Sex-­‐linked  genes  follow  specific  paZerns  of  inheritance  •  May  either  be  x-­‐linked  or  y-­‐linked  

Sex-­‐Linked  Disorders  

•  Some  recessive  alleles  found  on  the  X  chromosome  in  humans  cause  certain  types  of  disorders.  

 

– Color  blindness    

– Duchenne  muscular  dystrophy    

– Hemophilia  

Fig. 15-7

(a)   (b)   (c)  

XNXN   XnY   XNXn  ×   ×   XNY   XNXn   ×   XnY  

Y  Xn  Sperm  Y  XN  Sperm  Y  Xn  Sperm  

XNXn  Eggs   XN  

XN   XNXn  

XNY  

XNY  

Eggs   XN  

Xn  

XNXN  

XnXN  

XNY  

XnY  

Eggs   XN  

Xn  

XNXn  

XnXn  

XNY  

XnY  

Sex-Linked Genes

What  differences  do  you  note  in  the  two  karyotypes  below?    

X  inac%va%on  in  Female  Mammals  

•  In mammalian females, one of the two X chromosomes in each cell is randomly inactivated during embryonic development.

•  The inactive X condenses into a Barr body. •  If a female is heterozygous for a particular gene

located on the X chromosome, she will be a mosaic for that character.    

Fig. 15-8 X chromosomes

Early embryo:

Allele for orange fur

Allele for black fur

Cell division and X chromosome inactivation Two cell

populations in adult cat:

Active X Active X Inactive X

Black fur Orange fur

Athletes: Blood Doping and Barr Bodies (NY Times Article)

•  Neither  Tim  nor  Rhonda  has  Duchenne  muscular  dystrophy,  but  their  firstborn  son  does  have  it.  What  is  the  probability  that  a  second  child  of  this  couple  will  have  the  disease?    – ¼;  ½  chance  that  the  child  will  inherit  a  Y  chromosome  from  the  father  and  be  male  x  ½  chance  that  he  will  inherit  the  X  carrying  the  disease  from  his  mother.  

•  What  is  the  probability  if  the  second  child  is  a  boy?  A  girl?    Boy:  ½  chance  Girl:  Zero  chance:  ½  chance  of  being  a  carrier  

How  Linkage  Affects  Inheritance  

•  Morgan’s  Further  ExperimentaAon  

– Crossed  flies  that  differed  in  traits  of  two  different  characters.  

 

•  Determined  that  genes  that  are  close  together  on  the  same  chromosome  are  linked  and  do  not  assort  independently.  

 

–  Unlinked  genes  are  either  on  separate  chromosomes  or  are  far  apart  on  the  same  chromosome  and  assort  independently.  

Note  The  Difference  

•  Sex-­‐Linked  Gene:  a  single  gene  on  a  sex  chromosome.  

•  Linked  Genes:  two  or  more  genes  on  the  same  chromosome  that  tend  to  be  inherited  together.    – Results  deviate  from  Mendelian  GeneAcs  – Why?  Do  not  follow  the  Law  of  Independent  Assortment  

Recombina%on  of  Unlinked  Genes:  Independent  Assortment  of  Chromosomes  

•  When  Mendel  followed  the  inheritance  of  two  characters,  he  observed  that  some  offspring  have  combinaAons  of  traits  that  do  not  match  either  parent  in  the  P  generaAon.  

 

•  Recombinant  offspring  are  those  that  show  new  combinaAons  of  the  parental  traits.  

 

– When  50%  of  all  offspring  are  recombinants  geneAcists  say  that  there  is  a  50%  frequency  of  recombina%on.  

Recombination of Linked Genes: Crossing Over

•  Genes can be linked, but the linkage was incomplete, as evident from recombinant phenotypes

•  Some process must sometimes break the physical connection between genes on the same chromosome

•  That mechanism was the crossing over of homologous chromosomes

Copyright © 2008 Pearson Education Inc., publishing as Pearson Benjamin Cummings

Animation: Crossing Over

Fig. 15-10b

Testcross  offspring  

965  Wild  type  

(gray-­‐normal)  

944  Black-­‐  ves%gial  

206  Gray-­‐  

ves%gial  

185  Black-­‐  normal  

b+ vg+

b vg   b vg

b vg   b+ vg

b vg  

b vg

b+ vg+

Sperm  b vg

Parental-­‐type  offspring   Recombinant  offspring  

Recombina%on  frequency   =  

391  recombinants  2,300  total  offspring  

×  100  =  17%  

b vg  

b+ vg b vg+  

b vg+

Eggs  

Recombinant  chromosomes  

•  A linkage map is a genetic map of a chromosome based on recombination frequencies

•  Distances between genes can be expressed as map units; one map unit, or centimorgan (cM), represents a 1% recombination frequency

•  Map units indicate relative distance and order, not precise locations of genes

Copyright © 2008 Pearson Education Inc., publishing as Pearson Benjamin Cummings

Fig. 15-11

RESULTS: GENETIC MAP Recombination

frequencies

Chromosome 9% 9.5%

17%

b cn vg

•  Genes that are far apart on the same chromosome can have a recombination frequency near 50%

•  Such genes are physically linked, but genetically unlinked, and behave as if found on different chromosomes

Copyright © 2008 Pearson Education Inc., publishing as Pearson Benjamin Cummings

Recombina%on  of  Linked  Genes:  Crossing  Over  

•  Morgan  proposed  that    

–  Some  process  must  occasionally  break  the  physical  connecAon  between  genes  on  the  same  chromosome.  

 

–  Crossing  over  of  homologous  chromosomes  was  the  mechanism.  

 

•  Linked  genes  exhibit  recombinaAon  frequencies  less  than  50%.    

Abnormal  Chromosome  Number  

•  When  nondisjunc%on  occurs  pairs  of  homologous  chromosomes  do  not  separate  normally  during  meiosis.  

 

– Gametes  contain  two  copies  or  no  copies  of  a  parAcular  chromosome.  

 

•  Aneuploidy  results  from  the  ferAlizaAon  of  gametes  in  which  nondisjuncAon  occurred.  

 

–  Is  a  condiAon  in  which  offspring  have  an  abnormal  number  of  a  parAcular  chromosome  

Abnormali%es  Con%nued  

•  If  a  zygote  is  trisomic    

–  It  has  three  copies  of  a  parAcular  chromosome    

•  If  a  zygote  is  monosomic    

–  It  has  only  one  copy  of  a  parAcular  chromosome    

•  Polyploidy    

–  Is  a  condiAon  in  which  there  are  more  than  two  complete  sets  of  chromosomes  in  an  organism  

Altera%ons  of  Chromosome  Structure  

•  Breakage  of  a  chromosome  can  lead  to  four  types  of  changes  in  chromosome  structure  

 

– DeleAon    – DuplicaAon    –  Inversion    – TranslocaAon  

Human  Disorders  Due  to  Chromosomal  Altera%ons  

•  AlteraAons  of  chromosome  number  and  structure  

 – Are  associated  with  a  number  of  serious  human  disorders  

 •  Down  syndrome  is  usually  the  result  of  an  extra  chromosome  21,  trisomy  21  

Aneuploidy  of  Sex  Chromosomes  •  NondisjuncAon  of  sex  chromosomes  produces  a  variety  of  aneuploid  condiAons  – Klinefelter  syndrome  is  the  result  of  an  extra  chromosome  in  a  male,  producing  XXY  individuals  

•  Not  inherited:  non-­‐disjuncAon  occurs  during  meiosis  –  InferAlity  –  Do  not  produce  as  much  testosterone  as  usual  –  Smaller  testes  and  penis  –  Breast  growth  –  Less  facial  and  body  hair  –  Reduced  muscle  tone  –  Narrower  shoulders  and  wider  hips  – Weaker  bones  –  Decreased  sexual  interest  –  Lower  energy  

Aneuploidy  of  Sex  Chromosomes  Turner  syndrome  is  the  result  of  monosomy  X,  

producing  an  X0  karyotype.  •  1  in  every  2500  live  births  •  1%  of  fetuses  with  only  one  X  chromosome  survive  to  term    

•  Approximately  10%  of  all  miscarriages  are  due  to  Turner  syndrome.  

•  The  most  common  features  include  short  stature  and  gonadal  dysgenesis  

•  The  average  adult  height  of  a  woman  with  Turner  syndrome  is  4’8”  

•  StaAsAcs  found  through  the  Turner  Syndrome  Society  in  the  US  website  

 

Linda  Hunt  •  4’9  •  NCIS  •  “Grandmother  Willow”  

Disorders  Caused  by  Structurally  Altered  Chromosomes  

•  Cri  du  chat  is  a  disorder  caused  by  a  deleAon  in  a  chromosome  

 

•  Certain  cancers  are  caused  by  translocaAons  of  chromosomes  

Excep%ons  

•  Some  inheritance  paZerns  are  excepAons  to  the  standard  chromosome  theory  

 – Two  normal  excepAons  to  Mendelian  geneAcs  include  

 •  Genes  located  in  the  nucleus    •  Genes  located  outside  the  nucleus  

Genomic  Imprin%ng  

•  In  mammals,  the  phenotypic  effects  of  certain  genes  depend  on  which  allele  is  inherited  from  the  mother  and  which  is  inherited  from  the  father.  

 – Genomic  imprinAng  involves  the  silencing  of  certain  genes  that  are  “stamped”  with  an  imprint  during  gamete  producAon  

Genomic Imprinting

•  Allele has different effects depending on if it was inherited from the mother or the father

•  Example: Prader Willi vs. Angelman Syndrome

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Inheritance  of  Organelle  Genes  

•  Extranuclear  genes  are  genes  found  in  organelles  in  the  cytoplasm  

 

– The  inheritance  of  traits  controlled  by  genes  present  in  the  chloroplasts  or  mitochondria  depends  solely  on  the  maternal  parent  because  the  zygote’s  cytoplasm  comes  from  the  egg  

 

•  Some  diseases  affecAng  the  muscular  and  nervous  systems  are  caused  by  defects  in  mitochondrial  genes  that  prevent  cells  from  making  enough  ATP  

Organelle Genes

•  Extranuclear genes (cytoplasmic genes) •  Mitochondrial genes •  Maternal Inheritance! •  Example: Mitochondrial Myopathy

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