Human

 Genetics
Human  Chromosomes:  Genotypes/Phenotypes
 Lecture
objectives

By  the  end  of  this  lecture,  the  students  should  be  able  to:
1-­‐Describe  the  number,  structure,  and  classification  of  human  chromosomes.
2-­‐Explain  what  a  Karyotype  is  and  how  it  is  obtained.  
3-­‐Explain  Genotype  and  Phenotype
4-­‐Describe  chromosomal  banding  and  explain  its  use.
5-­‐Describe  the  process  of  in  situ  hybridization  and  the  information  it  provides
 Only  the  
Gene Expression folded  
protein  can
  Not e : c
t
e
h
ll
e
m
c o
a
d
chinery
e making
copies
lecule.  
perform   an m R N A m o
i o n )  This
function. (Tra n sc r ip t
the
moves into
.
cytoplasm
o s o m e s read the
Rib rately
Chromosome  in   Gene  in   a n d a c c u
Nucleus  in  cell
nucleus chromosome
Gene  has  DNA code
in a m in o acids
jo
th e r t o m a ke a
toge tion)
. ( T ra n sla
protein

For  further  explanation:  

https://m.youtube.com/watch?
v=OEWOZS_JTgk
 Eukaryotic cells
* Eukaryotic  cells  present  in  humans  and  some  other  
micro-­‐organisms  eg.Parasite  and  fungi
*There  are  two  types  of  organelles  :

-Membranous organelles -Non-membranous organelles

like : :
-­‐Mitochondria   -­‐Cytoskeleton  
-­‐Nucleus   -­‐Microvilli  
-­‐Endoplasmic  reticulum  (ER)   -­‐Centrioles  
-­‐Golgi  apparatus   -­‐Cilia  
-­‐Lysosomes   -­‐Flagella  
-­‐Peroxisomes -­‐Ribosomes
 Chromosomes:

1- carry genetic material (On  the  form  of  DNA)  

2-heredity: each pair of homologues

consists of one paternal and one
maternal chromosome  

3- The intact set is passed to each

daughter cell at every mitosis
 The Structure of chromosome:
chromosome
Order Of DNA coiling and folding :

1-­‐Primary  coiling:  DNA  double  helix.  

2-­‐Secondary  coiling:  around  histones  
(basic  proteins)  nucleosomes  
3-­‐Tertiary  coiling:    chromatin  fiber  
-­‐Chromatin  fibers  form  long  loops  on  
non-­‐histone  proteins        tighter  coils  
 chromosome.
in g   t h e   p rotein  
*fold
ive  
makes  it  act
es  are  
primary coiling *The  histon
Tertiary
o s it iv e ly   c h arged  
p
coiling
the  DNA  is  
e g a t iv e ly   c harged
n
Chromosome  structure:  
secondary coiling https://www.youtube.com/watch?v=zf7tbymrv9o
 Genes
■  Cytogenetics:    

The  study  of  the  structure  and  function  of  chromosomes  and  
chromosome  behaviour  during  somatic  and  germline  division  

 ■  Molecular  genetics:    

The  study  of  the  structure  and  function  of  genes  at  a  molecular  level  
how  the  genes  are  transferred  from  generation  to  generation
8
Mitotic cell cycle
G1  Phase  :  It  takes  about  10-­‐12  hrs  (Growth  and  normal  
*Interphase is the longest stage* metabolic  activity)    
S  Phase  :  It  takes  about  6-­‐8  hrs  (DNA  replication)  
G2  Phase  :  It  takes  about  2-­‐4  hrs  (Preparation  for  mitosis)  
Mitotic  Phase  :  Prophase,  Metaphase,  Anaphase  and  
Telophase
 Procedure of Chromosome Preparation
from Peripheral Blood
n
Trypsin : A
at
enzyme th
he
removes t
proteins .
o rd e r o f
*know the
the steps

Culture media
contains
Phytohemagglutinin
to stimulate T
lymphocytes to
divide

A  visual  demonstration  for  Karyotyping:    

https://youtu.be/7ShPzzrCetE
KARYOTYPE  :  The  number  and  appearance  of  
chromosomes  in  the  nucleus  of  a  eukaryotic  cell
 Chromatid
Chromatin
Karyotyping Protein + DNA
Sister chromatid

Based on:
1_ the length
2_ the position of the centromere ‫ﺻﺑﻐﻳﯾﺎﺕت ﻣﺗﻣﺎﺛﻠﺔ‬
3_ the presence or absence of satellites Centromere
Homologous
Chromosome

i n e to c h o r e  can  
The  k m o s omes  
  c h r o
adhere  the Chromosome
e   s p i n d l e  fibers  .  
to  th
th e   l en g th   o f  the   ‫ﺍاﻟﺻﺑﻎ‬
o m e  d o e s  NOT  
chromos
 the  
mean  that  g oing  to  
s o m e  i s
chromo
a v e   m o r e  GENES.  
h
 Karyotype:
A  series  of  steps  involved  :

1-­‐Culturing  
2-­‐Harvesting  
3-­‐Slide-­‐Making  
4-­‐Banding  
5-­‐Staining  
6-­‐Karyotyping  
7-­‐Chromosome  Analysis
 Centromeric position and arm length
P

The  ratio  of  the  lengths  of  the  two  arms  is  constant  for  each  chromosome.  
This  ratio  is  an  important  parameter  for  chromosome  identification  and  
allows  classification  of  chromosomes  into  several  basic  morphologic  types:  
 i-­‐metacentric                                          ii-­‐sub-­‐metacentric                                          iii-­‐acrocentric  
In  the  human  karyotype  chromosome  pairs  13,  14,  15,  21,  22  are  acrocentric  
 Metaphase chromosomes:
■  The  2  sister-­‐chromatids  
 are  principally  held  together  at  the  centromeric  region.  

■  Each  chromosome  has  a  centromere  (CEN),    

region  which  contains  the  kinetochore,  

■  CEN  divides  the  chromosome  into  two  arms:  

 the  short  arm  (p  arm)  and  the  long  arm  (q  arm).  

■  Each  arm  terminates  in  a  telomere.

 Phenotype
(Colour) Genotype:  
Genetic  constitution  of  a  cell,  an  organism,  
or  an  individual,  that  is  the  specific  allele  
makeup  of  the  individual  
Phenotype:  
PP A  phenotype  is  any  observable  
characteristic  of  an  organism,  such  as  its  
morphology,  development,  biochemical  or  
Genotype physiological  properties,  or  behavior
(Genetic make up)
Alleles:  One  of  the  alternative  versions  of  a  
gene  at  a  given  location  (locus)  along    a        
chromosome.    
An  individual  inherits  two  alleles  from  each  
parent.  

otype has
*Every phen
alleles
two parallel
the
(genotype),
ele
dominant all
e two alleles
between th
at is going
is the one th
the
to determine
is
features of th
phenotype .
 The  human  albino  gene  has  two  allelic  forms,  
Dominant  A  and  Recessive  a  .  
So,  there  are  three  possible  genotypes  :
AA  :  Homozygous  dominant.  
Aa  :  Heterozygous  .  
aa:  Homozygous  recessive.

Chromosomal  classification  : Items  in  the  description  of  Karyotype:

22  pairs  Autosomes,  from  1  –  22   Normal  Karyotypes:  

by  order  of  decreasing  length.     46,XY  
1  pair  of  sex  chromosomes:   46,XX  
XX  for  FEMALE.   Abnormal  karyotypes:  
XY  for  MALE. 47,XY,+21  
 Banding *In the nome
nclature
we
of the bands,
om the
should start fr
P) is
❖Certain staining techniques cause the chromosomes to take centromere.(
g the
used in namin
ent, (Q)
on a banded appearance shorter segm
is used in nam
ing the
longer one
❖Each arm presenting a sequence of dark and light bands .

❖Patterns are specific and repeatable for each chromosome,

❖Allowing accurate identification and longitudinal mapping for

locating gene positions and characterising structural changes.
❖Patterns, and the nomenclature for defining positional
mapping have been standardised .
 Chromosome  Banding
Band  resolution  
=

Estimate  of  number  of  

light  +  dark  bands  per  
haploid  set  of  
chromosomes.

More  Numbers  »  
More  Resolution      
400  »  550    »    850
 Chromosome  Banding: G  =  Giemsa  
vers  of  
R  =  Reverse  (re
G-­‐bands)  
.  
Q  =  Quinicrine
c  
G Banding: R Banding: C  =  Centromeri
tin.
heterochroma
Treat with trypsin and then heat and then treat with
with Geimsa Stain. Geimsa stain.

Q Banding: C Banding:
Treat with Quinicrine dye Staining of the Centromere.
giving rise to fluorescent Treat with acid followed by
bands. It requires an alkali prior to G banding.
ultraviolet fluorescent
microscope.
 Banded Karyotype:
Normal Banded Karyotypes :

A normal G-banded A normal R-banded

male Karyotype male Karyotype
 Philadelphia-chromosome translocation

Critical  genetic  event  in  the  

development  of  CHL(chronic  
myelogenous  leukemia).  

Due  to  a  cytogenetic  

abnormality  (translocation  
between  9  and  22).  
 Fluorescence In-Situ Hybridization (FISH)

- Using Fluorescent probe that binds with its complementary target sequence.
- They can be to study chromosomes in metaphase or interphase.

Usage : to determine chromosomal abnormalities, e.g. mutations,

e   hyb rid iz ation   aneuploidy, .
Th
een  
occurs  betw ’s  
DNA
one  of  the  
 the  
strands  and
probe.  
idy : An
*Aneuplo mber of
nu
abnormal
mes.
chromoso

FISH  of  interphase  nuclei  with  a  

FISH  of  metaphase  with  a  probe  for  
chromosome  21  centromeric  probe  
telomere  showing  signals  at  the  end  
showing  3  signals  consistent  with  
of  each  chromatid
trisomy  21
 ‫‪Team  Members:‬‬

‫طالل‪  ‬العبيواني‪  ‬‬ ‫نورة‪  ‬الخراز‪  ‬‬

‫لولوه‪  ‬الصغير‪  ‬نايف‪  ‬السلمي‪  ‬‬
‫علي‪  ‬العمر‪  ‬‬ ‫كيان‪  ‬كعكي‪  ‬‬
‫منيرة‪  ‬الحسن‪  ‬عمر‪  ‬سميا‪  ‬‬
‫عمر‪  ‬العيسى‪  ‬‬ ‫آية‪  ‬غانم‪  ‬‬
‫‪email:  [email protected]‬‬
‫شهد‪  ‬العنزي‪  ‬‬
‫مليس‪  ‬آل‪  ‬تميم‪  ‬‬ ‫ال‪  ‬تسكن‪  ‬بلدا ٌ‪  ‬ال‪  ‬يكون‪  ‬فيه‪  ‬عالم‪  ‬يفتيك‪  ‬في‪  ‬‬
‫دينك‪  ‬وال‪  ‬طبيب‪  ‬ينبئك‪  ‬عن‪  ‬أمر‪  ‬بدنك‪  ..‬‬
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