# α- and β-globin gene clusters on chromosomes 16 and 11.

❖ Deletions:
▪ Hereditary neuropathy with liability to pressure palsies
▪ Becker muscular dystrophy (in-frame deletion).
❖ Insertions:
▪ Hereditary sensory and motor neuropathy type 1a (repeat expansion)
▪ Myotonic dystrophy (MD) {CTG expansion (type 1 MD) or CCTG expansion}
▪ Progressive myoclonus epilepsy (EPM1) (dodecamer repeat expansion)
▪ Spinocerebellar ataxia type 10 (pentanucleotide repeat expansion)
▪ Becker muscular dystrophy (in-frame insertion).
❖ Synonymous or silent mutation

❖ Missense mutation: Many of the abnormal hemoglobins (Hb S, C, or E) are the result of
missense mutations.

▪ Sickle cell disease (a missense mutation in codon 6 of the β-globin gene produces
a substitution of valine for glutamic acid in the β-globin polypeptide)
Codon number
5 6 7 8
Normal allele: CCT GAG GAG AAG
Mutant allele: CCT GTG GAG AAG
▪ β-Thalassemia (Hb Indianapolis, a highly unstable β-globin)
▪ Hemophilia A (missense mutations in factor VIII gene; less severe)
▪ Familial hypercholesterolemia (mostly missense mutations of LDL receptor)
▪ Familial medullary thyroid carcinoma
▪ Multiple endocrine neoplasia type 2
▪ Alpha-1 antitrypsin deficiency
▪ Cystic fibrosis
▪ Marfan syndrome (mostly).

❖ Nonsense mutation:
▪ β-Thalassemia
▪ Hemophilia A (nonsense mutations in the factor VIII gene; more severe). These
result in a truncated protein product and little, if any, expression of factor VIII.
▪ Hirschsprung disease
▪ Cystic fibrosis.

❖ Frameshift mutation:
▪ Hb Tak, Hb Cranston, Hb Wayne, Hb McKees Rock
▪ Hemophilia A
▪ Cystic fibrosis
▪ Duchenne muscular dystrophy (DMD) (frameshift deletions or insertions)
▪ Pallister-Hall syndrome
▪ Sotos Syndrome.
Also 9q34 microdeletion syndrome.
Loss-of-function mutation: Usually inherited in an autosomal or X-linked recessive manner.
Hirschsprung disease.

Haplo-insufficiency mutation: Familial hypercholesterolemia (p. 175), acute

intermittent porphyria (p. 179), angioneurotic edema.

Gain-of-function mutation: Are dominantly inherited. Charcot-Marie-Tooth disease,

hereditary motor, and sensory neuropathy type I (p. 296), Huntington disease (p. 293),
specific tumors (p. 212), achondroplasia (p. 93) or Waardenburg syndrome type I (p. 91),
familial medullary thyroid carcinoma, multiple endocrine neoplasia type 2 (p. 100).

Dominant-negative mutation: Particularly common in proteins that are dimers or multimers,

for instance structural proteins such as the collagens, mutations in which can lead to
osteogenesis imperfecta.

Genotype-phenotype correlation:
o Mutations in the BRCA1BRCA1 gene = ovarian cancer, breast cancer (p. 224).
o Mutations in the receptor tyrosine kinase gene RET = loss-of-function nonsense
mutations lead to Hirschsprung disease, whereas gain-of-function missense mutations
result in familial medullary thyroid carcinoma or one of the two types of multiple
endocrine neoplasia type 2 (p. 100).
o Mutations in the LMNA gene are associated with an even broader spectrum of disease
(p. 112).

BER = autosomal recessive form of colorectal cancer (p. 223).

Post-replication repair = hereditary breast cancer (p. 224).

The ATM protein is involved in sensing DNA damage and has been described as the
‘guardian of the genome’. Mutations in the ATM gene cause ataxia telangiectasia (see p.
204), characterized by hypersensitivity to radiation and a high risk of cancer.
A gene map of the human genome with examples of some of the more common or important
single genes and disorders:
α1-AT 14q32 α1-Antitrypsin deficiency
ABO 9q34 ABO blood group
ACTH 2p25 Adrenocorticotrophic hormone deficiency
ADA 20q13.11 Severe combined immunodeficiency, ADA deficiency
AHP 9q34 Acute hepatic porphyria
AIP 11q23.3 Acute intermittent porphyria
AKU 3q2 Alkaptonuria
ALD Xq28 Adrenoleukodystrophy
APKD1 16p13 Adult polycystic kidney disease, locus 1
APKD2 4q21–23 Adult polycystic kidney disease, locus 2
APOB 2p24 Apolipoprotein B
APOE 19q.13.2 Apolipoprotein E
ARG1 6q23 Arginase deficiency, argininemia
ARSB 5q11–13 Mucopolysaccharidosis type VI, Maroteaux-Lamy syndrome
AS 15q11–13 Angelman syndrome
ATA 11q22.3 Ataxia telangiectasia
ATIII 1q23–25 Antithrombin III
ATRX Xq13 α-Thalassemia mental retardation
AZF Yq11 Azoospermia factor
BBS2 16q21 Bardet–Biedl syndrome
BLM 15q26.1 Bloom syndrome
BRCA1 17q21 Familial breast/ovarian cancer, locus 1
BRCA2 13q12.3 Familial breast/ovarian cancer, locus 2
BWS 11p15.4 Beckwith–Wiedemann syndrome
C3 19p13.2-13.3 Complement factor 3
C5 9q34.1 Complement factor 5
C6 5p13 Complement factor 6
C7 5p13 Complement factor 7
C9 5p13 Complement factor 9
CAH1 6p21.3 Congenital adrenal hyperplasia, 21-hydroxylase
CBS 21q22.3 Homocystinuria
CEP 10q25.2-26.3 Congenital erythropoietic porphyria
CFTR 7q31.2 Cystic fibrosis transmembrane conductance regulator
CKN2 10q11 Cockayne syndrome 2, late onset
CMH1 14q12 Hypertrophic obstructive cardiomyopathy type 1
CMH2 1q3 Hypertrophic obstructive cardiomyopathy type 2
CMH3 15q22 Hypertrophic obstructive cardiomyopathy type 3
CMT1A 17p11.2 Charcot–Marie–Tooth disease type 1A
CMT1B 1q22 Charcot–Marie–Tooth disease type 1B
CMT2 1p35–36 Charcot–Marie–Tooth disease type 2
COL1A1 17q21.31-22 Collagen type I, α1 chain, osteogenesis imperfecta
COL1A2 7q22.1 Collagen type I, α2 chain, osteogenesis imperfecta
COL2A1 12q13.11-13.2 Collagen type II, Stickler syndrome
COL3A1 2q31 Collagen type III, α1 chain, Ehlers-Danlos syndrome type IV
CYP11B1 8q21 Congenital adrenal hyperplasia, 11β-hydroxylase
DAZ Yq11 Deleted in azoospermia
DFNB1/A3 13q12 Non-syndromic sensorineural deafness, first recessive, third
dominant locus
DM 19q13.2-13.3 Myotonic dystrophy
DMD/BMD Xp21.2 Dystrophin, Duchenne and Becker muscular dystrophy
DRPLA 12p13.1-12.3 Dentatorubropallidoluysian disease
EDSVI 1p36.2-36.3 Ehlers-Danlos syndrome type VI
EYA1 8q13.3 Brachio-otorenal syndrome
F5 1q23 Coagulation protein V
F7 13q34 Coagulation protein VII
F8 Xq28 Coagulation protein VIII, hemophilia A
F9 Xq27.1-27.2 Coagulation protein IX, Christmas disease, hemophilia B
F10 13q34 Coagulation protein X
F11 Xq27.1-27.2 Coagulation factor XI
F12 5q33-qter Coagulation factor XII
FAP 5q21-22 Familial adenomatous polyposis, Gardner syndrome
FBN1 15q21.1 Fibrillin-1, Marfan syndrome
FBN2 5q23-31 Fibrillin-2, contractural arachnodactyly
FGFR1 8p11.1-11.2 Fibroblast growth factor receptor 1, Pfeiffer syndrome
FGFR2 10q26 Fibroblast growth factor receptor 2, Crouzon, Pfeiffer, Apert
syndrome
FGFR3 4p16.3 Fibroblast growth factor receptor 3, achondroplasia, thanatophoric
dysplasia
FH 19p13.1-13.2 Familial hypercholesterolemia
FRAXA (FMR1) Xq27.3 Fragile X mental retardation
FRDA 9q13–21.1 Friedreich ataxia
FSHMD 4q35 Facioscapulohumeral muscular dystrophy
GAL 9p13 Galactosemia
GAP 9q31 Basal cell nevus syndrome, Gorlin syndrome
GLB1 3p21.33 GM1 gangliosidosis
G6PD Xq28 Glucose-6-phosphate dehydrogenase
GUSB 7q21.11 Mucopolysaccharidosis type VII, Sly syndrome
HbB 11p15.5 β-Globin gene
HD 4p16.3 Huntington disease
HEXA 15q23–24 Hexosaminidase A, Tay-Sachs disease
HEXB 5q13 Hexosaminidase B, Sandhoff disease
HFE 6p21.3 Hemochromatosis
HGPRT Xq26-27.2 Hypoxanthine guanine phosphoribosyl transferase, Lesch-Nyhan
syndrome
HLA 6p21.3 Major histocompatibility locus
HPE3 7q36 Holoprosencephaly
IDUA 4p16.3 Mucopolysaccharidosis type I, Hurler syndrome
IGKC 2p12 Immunoglobulin κ light chain
IGLC1 22q11 Immunoglobulin λ light chains
INS 11p15.5 Insulin-dependent diabetes mellitus type 2
KRT5 12q11-13 Epidermolysis bullosa simplex, Koebner type
LGMD7 5q31 Limb-girdle muscular dystrophy
MCAD 1p31 Acyl coenzyme-A dehydrogenase, medium chain
MDS 17p13.3 Miller-Dieker lissencephaly syndrome
MEN1 11q13 Multiple endocrine neoplasia syndrome type 1
MHS 19q13.1 Malignant hyperpyrexia susceptibility, locus 1
MITF 3p14.1 Waardenburg syndrome type 2
MJD 14q24.3-31 Machado-Joseph disease, spinocerebellar ataxia type 3
MPS VI 5q11-13 Maroteaux-Lamy syndrome
MSH2 2p15-16 Hereditary non-polyposis colorectal cancer type 1
NCF2 1q25 Chronic granulomatous disease, neutrophil cytosolic factor-2
deficiency
NF1 17q11.2 Neurofibromatosis type I, von Recklinghausen disease
NF2 22q12.2 Neurofibromatosis type II, bilateral acoustic neuroma
NP 11p15.1-15.4 Niemann-Pick disease type A and B
NPC 18q11-12 Niemann-Pick disease type C
NPS 9q43 Nail-patella syndrome
OTC Xp21.1 Ornithine transcarbamylase
p53 17p13.1 p53 protein, Li-Fraumeni syndrome
PKU 12q24.1 Phenylketonuria
PROC 2q13-14 Protein C, coagulopathy disorder
PROS 3p11.1-q11.2 Protein S, coagulopathy disorder
PRNP 20p12-pter Prion disease protein
PWS 15q11 Prader-Willi syndrome
PXMP1 1p21–22 Zellweger syndrome type 2
RB 13q14.1-14.2 Retinoblastoma
RET 10q11.2 Familial medullary thyroid carcinoma, MEN 2A and 2B, familial
Hirschsprung disease
RH 1p34–36.2 Rhesus null disease, Rhesus blood group
RP1 8p11-q21 Retinitis pigmentosa, locus 1
RP2 Xp11.3 Retinitis pigmentosa, locus 2
RP3 Xp21.1 Retinitis pigmentosa, locus 3
rRNA Ribosomal RNA
SCA1 6p23 Spinocerebellar ataxia, locus 1
SCA2 12q24 Spinocerebellar ataxia, locus 2
SPH1 14q22-23.2 Spherocytosis type I
SMA 5q12.2-13.3 Spinal muscular atrophy
SOD1 21q22.1 Superoxide dismutase, familial motor neuron disease
SRY Yp11.3 Sex-determining region Y, testis-determining factor
TBX5 12q21.3-22 Holt-Oram syndrome
TCOF1 5q32-33.1 Treacher-Collins syndrome
TRPS1 8q24.12 Trichorhinophalangeal syndrome
TSC1 9q34 Tuberous sclerosis, locus 1
TSC2 16p13.3 Tuberous sclerosis, locus 2
TYR 11q14-21 Oculocutaneous albinism
USH1A 14q32 Usher syndrome type IA
USH1B 11q13.5 Usher syndrome type IB
USH1C 11p15.1 Usher syndrome type IC
USH2 1q41 Usher syndrome type II
VWS 1q32 van der Woude syndrome
VHL 3p25–26 von Hippel-Lindau syndrome
VWF 12p13.3 von Willebrand disease
WD 13q14.3-21.1 Wilson disease
WRN 8p11.2-12 Werner syndrome
WS1 2q35 Waardenburg syndrome type 1
WT1 11p13 Wilms tumor 1 gene
ZWS1 7q11.23 Zellweger syndrome type 1
Autosomal dominant inheritance

Features:
o Defect in autosome
o Males and females are equally affected (sex ratio equal)
o Expressed in heterozygous state (no carrier state)
o More severe or lethal in homozygous state
o Transmission is vertical
o Skipped generations are not typically seen
o Heterozygous affected individual mating with a homozygous normal individual →
recurrence risk is 50%
o If both parents are heterozygous → recurrence risk is 75%.

Examples
• Familial hypercholesterolemia (LDL receptor deficiency)
• Huntington disease
• Neurofibromatosis type 1
• Marfan syndrome
• Acute intermittent porphyria.

Autosomal recessive inheritance

Features:
o Defect in autosome
o Males and females are equally affected (sex ratio equal)
o Offspring must inherit one copy of the disease causing gene from each parent
o Expressed in homozygous state
o Heterozygous individuals are known as carriers
o Transmission is horizontal
o Typically seen in only one generation of a pedigree (skipped generations are
common)
o More common in consanguineous marriage
o If both parents are heterozygous (carrier): recurrence risk is 25%.

Examples:
• Sickle cell anemia
• Cystic fibrosis
• Phenylketonuria (PKU)
• Tay-Sachs disease (hexosaminidase A deficiency).
X-linked dominant inheritance

Features:
o Defect in X chromosome
o Both males and females are affected
o Expressed in heterozygous state (no carrier state but there may be incomplete
penetrance)
o Transmission is vertical
o Skipped generations are not typically seen
o Father can transmit affected gene to daughter only (no male-to-male transmission);
mother can transmit affected gene to either son or daughter
o If father is affected and mother is normal → none of the sons are affected but all of
the daughters are affected (assuming complete penetrance). If the sex of the fetus is
unknown, the recurrence risk is 50%
o If father is normal and mother is heterozygous affected: half of the sons will be
affected and half of the daughters will be affected.

Examples:
• Fragile X syndrome
• Vitamin D resistant rickets (X-linked hypophosphatemia)
• Most cases of Alport syndrome
• Incontinentia pigmenti
• X-linked dominant protoporphyria.
X-linked recessive inheritance

Features:
o Defect in X chromosome
o Usually males are affected, females are carriers (sex ratio unequal)
o Can be expressed in 45,X female
o Transmission is oblique
o Skipped generations are commonly seen
o Father can transmit affected gene to daughter only (no male-to-male transmission);
mother can transmit affected gene to either son or daughter
o If father is affected and mother is normal: all sons will be normal, all daughters will
be carriers
o If father is normal and mother is carrier: half of the sons will be affected and half of
the daughters will be carriers. If the sex of the fetus is unknown, the recurrence risk is
25%.

Common examples:
• Red-green color blindness
• Hemophilia A, hemophilia B
• DMD (Duchenne muscular dystrophy)
• BMD (Becker’s muscular dystrophy)
• G6PD deficiency (Glucose-6-phosphatase dehydrogenase deficiency)
• X-linked ichthyosis
• X-linked agammaglobulinemia.

Less common examples:

• X-linked mental retardation
• Alport syndrome
• Androgen insensitivity syndrome
• Charcot-Marie-Tooth disease
• Fabry disease
• Hunter’s syndrome
• Spinal and bulbar muscular atrophy
• Ornithine transcarbamylase deficiency
• Spinal muscular atrophy
• X-linked severe combined immunodeficiency.
Mitochondrial Inheritance

Mitochondrial DNA encodes 13 proteins involved in electron transport and oxidative

phosphorylation.
In addition, mitochondrial DNA encodes 22 transfer RNAs and 2 ribosomal RNAs.
Because a sperm cell contributes no mitochondria to the egg cell during fertilization,
mitochondrial DNA is inherited exclusively through females.

Features:
o Defect in mitochondrial DNA
o Both males and females are affected
o Transmission of the disease is only from a female
o All offspring of an affected female are affected
o None of the offspring of an affected male is affected
o Diseases are typically neuropathies and/or myopathies.

Examples:
• Leber hereditary optic neuropathy
• MELAS: mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes
• Myoclonic epilepsy with ragged red muscle fibers.
Types of chromosome abnormality
❖ Numerical
Aneuploidy
o Monosomy
o Trisomy
o Tetrasomy
Polyploidy
o Triploidy
o Tetraploidy
❖ Structural
Translocations
o Reciprocal
o Robertsonian
Deletions
Insertions
Inversions
o Paracentric
o Pericentric
Rings
Isochromosomes
❖ Different Cell Lines (Mixoploidy)
Mosaicism
Chimerism

Chromosome abnormalities
❖ Numerical abnormalities
o Monosomy: 45,X Turner syndrome (p. 277).
o Trisomy
▪ Down syndrome is often known as trisomy 21.
▪ Patau syndrome (trisomy 13) (p. 275) and Edwards syndrome (trisomy 18)
(p. 275).
▪ 47,XXX
▪ 47,XXY
▪ 47,XYY
o Polyploidy: 69, triploidy, or 92, tetraploidy
Cell cycle:

In rapidly dividing cells cell cycle lasts for between 16 and 24 hours. In rapidly dividing cells
such as those of epithelial tissue (found, for example, in the lining of the intestines and in the
lungs), the cycle may be completed in less than 10 hours. Other cells, such as those of the
liver, might divide only once each year or so.

G1 phase = Chromosomes become thin and extended. Synthesis of RNA and proteins takes
place. Cells that have stopped dividing, such as skeletal muscle cells and neurons, usually
arrest in this phase and are said to have entered a noncyclic stage known as G0.

S phase = DNA replication occurs and the chromatin of each chromosome is replicated. This
results in the formation of two chromatids, giving each chromosome its characteristic X-
shaped configuration.

G2 phase = Interphase is completed by a relatively short G2 phase during which the

chromosomes begin to condense in preparation for the next mitotic division.
Cells divide in response to important internal and external cues. Critical to regulation of the
cell cycle are cyclin-dependent kinases (CDKs), which phosphorylate other regulatory
proteins at key stages of the cell cycle. To carry out this function, the CDKs must form
complexes with various cyclins, proteins that are synthesized at specific cell-cycle stages and
are then degraded when CDK action is no longer needed.
Faulty regulation of the cell cycle can lead to cancer.

The regulation of cell growth is accomplished by substances that include:

1. growth factors that transmit signals from one cell to another;
2. specific receptors for the growth factors;
3. signal transduction molecules that activate a cascade of phosphorylating reactions
within the cell; and
4. nuclear transcription factors.
The cell integrates and interprets the host of signals it receives from its environment.
Decisions to grow and divide, or to stop growing and differentiate, result from processing of
these signals.
Activators of cell cycle
• Growth factors
• Cyclin-CDK complexes (inactivates pRb by phosphorylating it)
• MDM2 (binds to and degrades p53)
• E2F transcription complex
• bcl-2 oncogene (by inhibiting apoptosis)

Repressors of cell cycle

• p14 (binds to and inhibits MDM2)
• p16, p21 (inactivate CDKs)
• p53 (by acting through p21), also induce apoptosis in response to DNA damage
• pRb (by binding with E2F transcription complex halts the cell cycle before S phase
begins)

Cell-Cycle Factors
Cancer cells can increase in number by increased growth and division, or accumulate through
decreased cell death. In vivo, most cells are in a non-dividing state. Progress through the cell
cycle (p. 39) is regulated at two points: one in G1 when a cell becomes committed to DNA
synthesis in the S phase, and another in G2 for cell division in the M (mitosis) phase, through
factors known as cyclin-dependent kinases. Abnormalities in regulation of the cell cycle
through growth factors, growth factor receptors, GTPases or nuclear proteins, or loss of
inhibitory factors lead to activation of the cyclin-dependent kinases, such as cyclin D1,
resulting in cellular transformation with uncontrolled cell division. Alternatively, loss of the
factors that lead to normal programmed cell death, a process known as apoptosis (p. 85), can
result in the accumulation of cells through prolonged cell survival as a mechanism of
development of some tumors. Activation of the bcl-2 oncogene through chromosomal
rearrangements is associated with inhibition of apoptosis, leading to certain types of
lymphoma.
❖ Both DNA synthesis and RNA synthesis occurs in the 5′ to 3′ direction. That is, 5′ end is
synthesized first and 3’ end is synthesized last.
❖ Both DNA polymerase & RNA polymerase move in the 3′ to 5′ direction.
❖ In RNA synthesis:
• 5’ to 3’ strand = coding strand = sense strand = non-template strand
• 3’ to 5’ strand = noncoding strand = antisense strand = template strand
Transcription
1. RNA polymerase II binds to a promoter (a
nucleotide sequence that lies just
upstream of a gene) site near the 5′ end of
a gene on the DNA.
2. It then pulls a portion of the DNA strands
apart from each other, exposing
unattached DNA bases.
3. One of the two DNA strands provides the
template for the sequence of mRNA
nucleotides. This template DNA strand is
also known as the antisense strand.
4. RNA polymerase moves in the 3′ to 5′
direction along the DNA template strand,
assembling the complementary mRNA
strand from 5′ to 3′.
5. Soon after RNA synthesis begins, the 5′ end
of the growing RNA molecule is capped by
the addition of a chemically modified
guanine nucleotide. This 5′ cap appears to
help prevent the RNA molecule from being
degraded during synthesis, facilitates its
transport to the cytoplasm, protects it
from degradation by exonucleases,
facilitates attachment to the ribosomes,
and later it helps to indicate the starting
position for translation of the mRNA
molecule into protein.
6. Transcription continues until a group of
bases called a termination sequence is
reached. Near this point, a series of 100 to
200 adenine bases are added to the 3′ end
 of the RNA molecule. This structure,
known as the poly-A tail, may be involved
in stabilizing the mRNA molecule so that it
is not degraded when it reaches the
cytoplasm.
7. RNA polymerase usually continues to
transcribe DNA for several thousand
additional bases, but the mRNA bases that
are attached after the poly-A tail are
eventually lost.
8. Finally, the DNA strands and the RNA
polymerase separate from the RNA strand,
leaving a transcribed single mRNA strand.
This mRNA molecule is termed the
precursor mRNA or pre-mRNA or primary
mRNA.
9. Before this primary mRNA transcript leaves
the nucleus, non-coding introns are
removed by nuclear enzymes, and the
coding exons are spliced together to form
a shorter mature, functional mRNA that
will migrate to the cytoplasm. The excised
sequences are called introns, and the
sequences that are left to code for proteins
are called exons.
10. Then mature transcript moves out of the
nucleus into the cytoplasm.
❖ RNA processing (post-transcriptional
modification of nRNA) involves splicing,
capping, and polyadenylation.

❖ For mRNA splicing followings are needed:

• A 5′ donor GT dinucleotide and a 3′
acceptor AG dinucleotide
• Short splicing consensus sequences
• Branch site (another intronic sequence)
• small nuclear RNA (snRNA) and associated
proteins.
Translation
Each tRNA molecule has a site at the 3′ end
for the attachment of a specific amino acid by
a covalent bond. At the opposite end of the
cloverleaf is a sequence of three nucleotides
called the anticodon, which undergoes
complementary base pairing with an
appropriate codon in the mRNA.
The attached amino acid is then transferred
to the polypeptide chain being synthesized.
1. During translation the ribosome first binds
to an initiation site on the mRNA
sequence. This site consists of a specific
codon, AUG, which specifies the amino
acid methionine.
2. The ribosome then binds the tRNA to its
surface so that base pairing can occur
between tRNA and mRNA.
3. The ribosome moves along the mRNA
sequence, codon by codon, in the 5′ to 3′
a.direction.
4. As each codon is processed, an amino acid
is translated by the interaction of mRNA
and tRNA. In this process, the ribosome
provides an enzyme that catalyzes the
formation of covalent peptide bonds
 between the adjacent amino acids,
resulting in a growing polypeptide.
5. When the ribosome arrives at a stop
codon on the mRNA sequence, translation
and polypeptide formation cease.
6. The amino (NH2) terminus of the
polypeptide corresponds to the 5′ end of
the mRNA strand, and the carboxyl
(COOH) terminus corresponds to the 3′
end.
7. After synthesis is completed, the mRNA,
the ribosome, and the polypeptide
separate from one another.
8. The polypeptide is then released into the
cytoplasm.
Before a newly synthesized polypeptide can
begin its existence as a functional protein, it
often undergoes further processing, termed
posttranslational modification. These
modifications can take a variety of forms,
including proteolytic cleavage into smaller
polypeptide units (e.g., the conversion of
proinsulin to insulin) or combination with
other polypeptides to form a larger protein.
Other possible modifications include chemical
modification of amino-acid side chains (e.g.,
hydroxylation, methylation), the addition of
carbohydrate or lipid moieties (e.g.,
glycosylation). Such modifications may be
needed, for example, to produce proper
folding of the mature protein or to stabilize its
structure.
Before dividing, a cell must duplicate its contents, including its DNA; this occurs during
interphase. The alternation of mitosis and interphase is referred to as the cell cycle.
As Figure 2-19 shows, a typical cell spends most of its life in interphase. This portion of the
cell cycle is divided into three phases, G1, S, and G2. During G1 (gap 1, the interval between
mitosis and the onset of DNA replication), synthesis
of RNA and proteins takes place. DNA replication occurs
during the S (synthesis) phase. During G2 (the interval
between the S phase and the next mitosis), some DNA repair
takes place, and the cell prepares for mitosis. By the time G2
has been reached, the cell contains two identical copies of
each of the 46 chromosomes. These identical chromosomes
are referred to as sister chromatids. Sister chromatids often
exchange material during interphase, a process known as
sister chromatid exchange.
The cell cycle consists of the alternation of cell
division (mitosis and cytokinesis) and interphase.
DNA replication and protein synthesis
take place during interphase.

❖ Structural abnormalities
▪ Balanced reciprocal translocation involving the long arms of chromosomes 11 and 22
is relatively common. 11;22 translocation
▪ Robertsonian translocation is an unbalanced reciprocal translocation 14q21q
Robertsonian translocation

A Robertsonian translocation results from the breakage of

two acrocentric chromosomes (numbers 13, 14, 15, 21, and
22) at or close to their centromeres, with subsequent fusion
of their long arms (see Figure 3.19). This is also referred to
as centric fusion. the most common
being fusion of the long arms of chromosomes 13 and 14
(13q14q).

13q21q or a 14q21q Robertsonian translocation

21q21q Robertsonian translocation.
Risks in Robertsonian translocations:
Translocation Down Syndrome, birth of babies with Down syndrome as
a result of the embryo inheriting two normal number
21 chromosomes (one from each parent) plus a translocation
chromosome involving a number 21 chromosome
autosomal recessive disorder, such as sensorineural deafness.

14q21q Robertsonian
translocation in a child with Down syndrome.