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The Human Genome and Chromosomal Basis of Heredity and Chromosomal Disorders. Chromosomes were found to be the bearer of genetic factor. Ömer Faruk Bayrak. WHAT IS GENE?. 2005. 2003. DNA Double Helix, Watson & Crick Nature, 1953. Human genome Project.

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the human genome and chromosomal basis of heredity and chromosomal disorders

The Human Genome and Chromosomal Basis of Heredity and Chromosomal Disorders

Chromosomes were found to be the bearer of genetic factor

Ömer Faruk Bayrak





DNA Double Helix,

Watson & Crick

Nature, 1953

Human genome Project

Inactivation of different X genes

The physical and functional unit of heredity that carries information from one generation to the next
  • DNA sequence necessary for the synthesis of a functional protein or RNA molecule.
  • Gene were first detected and analyzed by Mendel and subsequently by many other scientist (Mendel stated that physical traits are inherited as “particles”)
  • Mendel did not know that the “particles” were actually Chromosomes & DNA
  • Subsequent studies shows the correlation betweentransmission of genes from one generation to generation (Segregation and independent assortment) and the behavior of chromosomes during sexual reproduction, specifically the reduction division of meiosis and fertilization.
  • These and related expt. provided a strong early evidence that genes are usually located on chromosomes.
What are the requirements to fulfill as a genetic material?
  • 1. The genotype function or replication:
      • The genetic material must be capable of storing genetic information and transmitting this information faithfully from parents to progeny, generation after generation.
  • 2. The phenotype function or gene expression
      • The genetic material must control the development of phenotype of the organism, be it a virus, a bacterium, a plant or animal.
      • That is, the genetic material must dictate the growth and differentiation of the organism from single celled zygote to the mature adult.
dna structure

Nucleic acids first called “nuclein” because they were isolated from cell nuclei by F. Miescher in 1869

  • Each nucleotide is composed of

(1) a Phosphate group

(2) a five – carbon sugar (or Pentose), and

(3) a cyclic nitrogen containing compound called a base.

In DNA, the sugar is 2-deoxyribose (thus the name deoxyribonucleic acid)

In RNA, the sugar is ribose (thus ribonucleic acid).


Adenine and Guanine are double ring base called Purines



Cytosine, thymine, and uracil are single-ring base called Pyrimidines.




chargaff s rule
Chargaff’s rule
  • The composition of DNA from many different organisms was analyzed by E.Chargaffand his colleagues.
  • It was observed that concentration of thyminewas always equal to the concentration of adenine (A = T)
  • And the concentration of cytosine was equalto the concentration of guanine(G = C).
  • This strongly suggest that thymine and adenine as well as cytosine and guanine were present in DNA with fixed interrelationship.
  • Also the total concentration of purines(A +G) always equal to the total concentration ofpyrimidine(T +C). However, the (T+ A)/ (G+C) ratio was found to vary widely in DNAs of different species.
did you know

The earth is 150 billion m

or 93 million miles from

the sun.

Did you know?
  • Each cell has about 2 m of DNA.
  • The average human has 75 trillion cells.
  • The average human has enough DNA to go from the earth to the sun more than 400 times.
  • DNA has a diameter of only 0.000000002 m.

DNA replication

After publishing their model, W&C made a hypothesis for the replication of DNA. 

a.  Hydrogen bonds break, and the two strands separate.

b.  Each strand now serves as a template for a new complimentary strand.

c.  Nucleotides are connected and the daughter DNA molecules are formed.


- Once hydrogen bonds begin to break, replication bubbles begin to form at points along the DNA strand.

- Bubbles form at sites called origins of replication. 

- DNA replication proceeds in both directions from the origin of replication.

human chromosomes
Human Chromosomes
  • Humans have 46 chromosomes organized as 23 pairs that are homologous because each pair contains the homologous genes
  • Humans are genetically diploid= 2 copies of each chromosome, except for the sex chromosomes (X+Y) that are non-identical
  • Each species has a characteristic set of chromosomes.
eukaryotic chromosome structure
Eukaryotic Chromosome Structure
  • Genetic material in eukaryotes is organized to form linear chromosomes

(one chromosome = one molecule)

  • Pulsed-field gel electrophoresis is used to separate individual chromosomes that migrate as distinct bands on a gel

(visible evidence for chromosomes)

chromatin fiber organization
Chromatin Fiber Organization
  • Dark field electron microscopy shows fiber structure of chromosomes as beads on a string
  • Nucleosome= the fundamental unit of organization of the chromatin fiber
  • Each nucleosome contains a core particleof basic proteins = histones surrounded by 1.75 turns of DNA helix = 145 bp of DNA
chromatin fiber structure
Chromatin Fiber Structure
  • Core particle histone octamer contains two molecules each of:

- histone H2A

- histone H2B

- histone H3

- histone H4

  • Linker region connecting nucleosomes contains histone H1
chromatin fiber structure1
Chromatin Fiber Structure
  • Primary Structure of DNA = double helix = 2nm duplex DNA
  • Duplex DNA winds around histone octamers to form nucleosomes= 11nmhistone fiber
  • Nucleosome fibers form left-handed helix with 6 nucleosomes per turn = 30 nm chromatin fiber (solenoid structure)

Organization of Nucleosomes

The DNA molecule is

wound one and three

fourths turns around a

histone octamer.


Various Stages of Chromosome Condensation


Model of


chromosome structure
Chromosome Structure
  • 30 nm chromatin fiber condenses to metaphase chromatid = 1400 nm
  • Nonhistone protein complexes =scaffold: Required for the attachment of loops of chromatin fibers

(confirmed by DNase digestion)

chromosome structure1
Chromosome Structure
  • Euchromatin= comprises most of the genome, transcriptionally active parts
  • Heterochromatin= highly condensed inactive chromatin located at centromeres and telomeres
  • Centromere= attachment point for sister chromatids and spindle fibers
  • Telomere= end of chromosome

Schematic Drawing of

Metaphase Chromosome

centromeres essential for chromosome segregation
Centromeres(Essential for chromosome segregation)
  • Centromeres = chromosome regions that contain the site of attachment for microtubules = kinetochore
  • Centromeres contain heterochromatin, condensed chromatin
  • In situ hybridization of metaphase chromosomes shows satellite DNA at centromeres
telomeres essential for the stability of the chromosomal tip
Telomeres(Essential for the stability of the chromosomal tip)
  • Telomeres are specialized regions of DNA at the ends of chromosomes
  • Telomeres contain short tandem DNA repeats that are added to ends by the enzyme = telomerase
  • Telomerase contains RNA primer complementary to telomere repeat
sex chromosomes
Sex Chromosomes
  • X and Y chromosomes = sex chromsomes which are non-identical but share some genes for pairing
  • Males are genetically haploid for most genes on the X chromosome which results in unique patterns of X-linked inheritance
  • Autosomes = non-sex chromosomes
cell division chromosome division cell cycle mammalian
Cell Division – Chromosome Division: Cell Cycle (Mammalian)
  • Cell division cycles occur in stages:

- G1 = pre-DNA synthesis

- S = DNA synthesis

- G2 = post-DNA synthesis

- M = mitosis: cell division occurs by precise steps which distribute one set of chromosomes to each of two daughter cells

  • Cell cycle takes about 18-24 hours in higher eukaryotes.
  • Mitosis takes about 1-2 hours.

Mitosis: Meiosis:


  • Chromosome replication: exact duplicates are made during the S period = sister chromatids formed (interphase).

-Stages of Mitosis-

  • Prophase- individual chromosomes become visible, spindle fibers organize and attach to centromeres of chromosomes
  • Metaphase- chromosomes line up in center of cell: alignment of chromosomes along the metaphase plate is a checkpoint to proceed to the next phase.
Anaphase- sister chromatids separate after centromere division: one member of each pair is pulled to either pole of the cell
  • Telophase- nuclei of two new cells reorganize; the cells are diploid = each contains both members of every pair of chromosomes

*Chromosomes decondense until they are no longer visible. *Cytokinesis follows.



Diploidity is


after mitosis.

  • Meiosisis a specialized type of cell division that occurs only in reproductive cells (e.g. eggs or sperms)
  • Two rounds of cell division result in the formation of gametes that are genetically haploid = contain only one copy of each pair of homologous chromosomes


<Simplified overview of meiosis>

*The behavior of a single pair of

homologous chromosomes.

*Each chromosomes already

consists of two chromatids,

joined at a single centromere.

  • Meiosis occurs in stages and requires two cell division events
  • Meiosis I:

- Chromosomes duplicate in S phase

- Homologous chromosomes pair: 4 strands of chromatids align

- Homologous chromosomes are pulled to either pole of the cell at anaphase

  • Meiosis II:

- Cell division occurs in the absence of chromosome duplication

- Sister chromatids separate at anaphase as in mitotic division


Major Stages of Meiosis with

Two Pairs of Homologous Chromosomes


Crossing-over (Chiasmasis) between

Homologous Chromosomes

* No cross-over between sister chromatids.

* Random genotype formation in a gamete

meiotic vs mitotic division
Meiotic vs. Mitotic Division
  • Meiosisproduces four cells, each of which contains one copy of each pair of homologous chromosomes =

genetically haploid (n)

  • Mitosis produces two cells that contain both members of each pair of homologous chromosomes = genetically diploid (2n)
Cytogenetic disorders are characterized by an abnormal constitutional karyotype

What mechanisms would result in cytogenetic abnormalities?

chromosomal rearrangments
Chromosomal Rearrangments
  • Translocation
  • Deletion
  • Duplication
  • Inversion
12 2 chromosome accidents

12.2Chromosome Accidents

Relate Down syndrome and the nonseparation of chromosomes

Describe how chromosomes can be damaged and the consequential effects

Explain how a “jumping gene” can affect other genes.

Use a microscope to observe different shapes and lengths of chromosomes

chromosomal aberrations
Chromosomal Aberrations
  • Changes in the numbers of chromosomes
    • Polyploidy
      • Extra complete sets of chromosomes
      • 3N, 4N, 5N, etc.
    • Aneuploidy
      • Extra or missing single chromosomes
      • 2N + 1, 2N -1, etc.
chromosomal aberrations1
Chromosomal Aberrations
  • Changes in structure
    • Changes in the number of genes
      • deletions: genes missing
      • duplications: genes added
chromosomal aberrations2
Chromosomal Aberrations
  • Changes in structure
    • Changes in the location of genes
      • inversions: 180o rotation
      • translocations: exchange
      • transpositions: gene “hopping”
      • Robertsonian changes: fissions or fusions
  • Having extra sets
    • 3N, 4N, etc.
  • Suffix: “-ploid” or “-ploidy”
    • 3N = triploid
    • 4N = tetraploid

N = A B C:

2N = AA BB CC:


N = A B C:


  • Monoploidy (haploidy): rare in animals
    • exceptions: Bees: males are haploid - develop from unfertilized eggs; females are diploid
  • More common in plants
    • alternation of generations increases occurrence of haploidy
haploidy in plants
Haploidy in Plants
  • Occasionally, unfertilized gamete may develop into adult plant
    • usually small, with lowered viability
    • sterile
3n or more in animals
3N or More in Animals
  • Most common form of polyploidy in animals is triploidy
    • arises from two sperm fertilizing the same egg
    • if the organism survives, it is sterile
      • pairing of homologues in meiosis is disrupted
    • Survival is extremely rare
3n or more in plants
3N or More in Plants
  • Polyploidy generally improves viability in plants
    • Plants are larger, produce larger flowers, more seeds, hardier, etc.
    • Pairing at meiosis is still a problem, especially w/ odd ploidies: 3N, 5N, 7N, etc.
      • May reproduce asexually
3n or more

Extra sets of chromosomes come from the same species

Arise from double fertilization usually

All chromosomes have homologues


Extra sets of chromosomes come from different species

Arise from hybridization

New chromosomes have no homologues

3N or More
allopolyploidy or hybridization
Allopolyploidy or hybridization

Horse + donkey  mule




N = 63


instant plant speciation through allo and autopolyploidy
Instant Plant Speciation Through Allo- and Autopolyploidy
  • Possible for entirely new species of plant to be created almost instantly
  • Hybridization (allopolyploidy) followed by autopolyploidy --> plant w/ totally different chromosomal make up from either parent
  • Fertile only w/ itself; NEW SPECIES
  • Extra single chromosomes or missing single chromosomes
    • 2N + 1
    • 2N - 1
  • Suffix: “-somy” or “-somic”
    • 2N + 1 = trisomy
    • 2N - 1 = monosomy
    • 2N + 2 = tetrasomy
  • Generally arise through non-disjunction at meiosis
    • homologues or chromatids do not separate
    • gametes contain 2 or no copies of one chromosome
aneuploidies in humans
Aneuploidies in Humans
  • Most aneuploidies in humans lead to such drastic effects, the fetus is spontaneously aborted early in development
  • A few survive ‘til birth; some beyond
Meiosis occurs repeatedly in a person's lifetime as the testes produce sperm or the ovaries complete production of eggs.
  • Almost always, the meiotic spindle distributes chromosomes to the daughter cells without error.
  • But occasionally an accident occurs that can have serious consequences.
down syndrome genotype
Down SyndromeGenotype
  • A normal human karyotype has 46 total chromosomes, or 23 pairs.
  • When a karyotype includes not two, but three number 21 chromosomes, this condition is called trisomy 21.
down syndrome
Down Syndrome
  • Trisomy 21 usually results from an error during but meiosis I.
  • In most cases, a human embryo with an abnormal number of chromosomes results in a miscarriage (meaning the embryo does not survive).
  • But many embryos with trisomy 21 do survive.
  • Trisomy 21 affects about one out of every 700 children born in the United States.
down syndrome1
Down Syndrome
  • People with trisomy 21 have a general set of symptoms called Down syndrome, named after John Langdon Down, who described the syndrome(set of symptoms) in 1866.
  • These symptoms include:
    • certain characteristic facial features
    • below-average height
    • heart defects
    • an impaired immune system
    • varying degrees of mental disability.

Though people with Down syndrome have lifetimes that are shorter than average, they can live to middle age or beyond.

nonseparation of chromosomes
Nonseparation of Chromosomes
  • Trisomy 21 and other errors in chromosome number are usually caused by homologous chromosomes or sister chromatids failing to separate during meiosis, an event called nondisjunction.
  • Nondisjunction can occur in anaphase of meiosis I or meiosis II, resulting in gametes with abnormal numbers of chromosomes.

What causes nondisjunction?

  • As women gets older, they are more likely to have offspring with trisomy 21.
  • Meiosis begins in the pre-egg cells in a girl's ovaries before she is born but then pauses until years later.
  • At puberty, meiosis resumes. Usually only 1 egg resumes meiosis and is released from the ovaries each month (ovulation) until menopause.
  • This means that a cell might remain stopped in the middle of meiosis for decades!!
  • It seems that the longer the time lag, the greater the chance that there will be errors such as nondisjunction when meiosis is finally completed.
  • Some researchers hypothesize that damage to the cell during this lag time contributes to errors in meiosis.
damaged chromosomes
Damaged Chromosomes
  • Even if all chromosomes are present in normal numbers in a cell, changes in chromosome structure may also cause disorders.
  • There are 4 types of chromosomal change
  • Duplication
  • Deletion
  • Inversion
  • Translocation
  • Part of a chromosome is repeated
  • Not always fatal, but often results in developmental abnormalities
  • Chromosome fragment is lost
  • If the fragment is part of a gene, the gene does not work
  • Potential for very serious effects
  • Fragment of original chromosome’s base sequence is reversed
  • Fragment of 1 chromosome attaches to a nonhomologous chromosome

Click here for some effects of chromosomal translocations…

jumping genes
Jumping Genes
  • Another type of change in chromosomes involves single genes that can move around. This startling discovery was the work of American geneticist Barbara McClintock (1902-1992) in the 1940s.
jumping genes1
Jumping Genes
  • While studying genetic variation in corn, McClintock found that certain genetic elements (genes) had the unusual ability to move from one location to another in a chromosome. They could even move to an entirely different chromosome. (Note that this is different from a translocation, where a whole piece of the chromosome moves, not just a gene.)
McClintock discovered that these "jumping genes" could land in the middle of other genes and disrupt them. For instance, jumping genes could disrupt pigment genes in corn cells, leading to spotted kernels.
  • McClintock's jumping genes are now called transposons.
  • Current evidence suggests that all organisms, including humans, have transposons.
  • In 1983, McClintock received a Nobel Prize for her pioneering work.
The transposon includes a gene that codes for an enzyme.
  • The enzyme catalyzes movement of the gene by attaching to the ends of the transposon and another site on the DNA.
  • The enzyme then cuts the DNA and catalyzes insertion of the transposon at the new site, sometimes disrupting another gene.

Some copy themselves and jump to new locations in our DNA where they affect adjacent genes. In their new location they can disrupt a gene completely, or subtly change the way it exerts its effects in the cell. This can have both positive and negative consequences.

Click here if you want to learn more…