Introduction to genetics (Unit - I)for B.Sc. Nursing Students

 During mid 19th Century, Gregor Mendel observed that certain
features pass from parents to their children/offspring.
 A child usually looks like their parents and is due to inheritance of
certain characteristics from parents to children .
 This transmission of characteristics from parents to children is
known as heredity.
 The basic unit of heredity is gene, which consist of portion of DNA
molecules.
 The term gene was coined by Johannsen in 1909.
INTRODUCTION

GENETICS
 Genetics is the study which deals with the science of genes,
heredity and its variations in living organism.
 Gregor Mendel is the father of Genetics
 The term Genetics was coined by William Bateson

 GENE
 ALLELES
 Dominant
 Recessive
 Chromosomes
Terminologies

 Gene is defined as a segment of DNA (Deoxyribonucleic Acid)
which carries the genetic information.
 Gene is the basic physical and functional unit of heredity
 DNA has also segment which do not contain gene.
 The human genome contains about 30000 – 40000 genes and each
gene varies in size.
Gene

 An allele is one of two, or more, forms of a given gene variant.
 Each allele determines a single inherited characteristics in an
individual.
Alleles

 Chromosomes are thread-like structures located inside the nucleus
of animal and plant cells. Each chromosome is made of protein and
a single molecule of deoxyribonucleic acid (DNA).
 Passed from parents to offspring, DNA contains the specific
instructions that make each type of living creature unique.
 The term chromosome comes from the Greek words for color
(chroma) and body (soma). Scientists gave this name to
chromosomes because they are cell structures, or bodies, that are
strongly stained by some colorful dyes used in research.
Chromosomes

PRACTICAL APPLICATIONS OF
GENETIC IN NURSING

 Nurses came across individuals or families affected by the genetic
diseases.
 Nurses are a vital links between patients and health care services.
 Nurses should have a basic sound knowledge of genetics.
 The important role of nurses in genetic include -
Role of Nurse in Genetics

 Interviewing patients or individuals with suspected genetic disorders
 Taking a detailed clinical history along with relevant family history
(over three generations) from patients or parents of child with
genetic disorder.
 Refer those with genetic disorder to the concerned doctor.
Genetic Counseling and
Interviewing

 Provide health education related to genetics and genetic testing.
 Drawing and interpreting a pedigree chart.
 Ability to recognize the possibility of a genetic disorder based on
the pedigree chart.
 Assessment of a genetic risk especially in conjugation with genetic
testing options.
Planning, Screening or Gene
Based Testing Programs

 Follow up of positive newborn screening test.
 Monitoring individuals with genetic disorders
 Working with families under stress due to a genetic disorder.
Monitoring

 Developing an individualized plan of care and services of affected
patient.
 Participating in public education about genetics.
 Maintain the privacy and confidentiality of the patients genetic
information.
Care

Genetic Aspect
 When a genetic condition is identified, it leads to stress and shock in the
individuals and his family.
 The nurses have a major role in counseling, reducing their fears, getting
the consent for genetic testing and arranging the tests and offering post test
advice.
About Transmission of genetic condition within families
 If an individual is identified to have a genetic condition, nurses should
educate the family members, who are likely to affected and advice
counseling and screening for them.
Educational Role

 Educate how genetics and environmental factors influence health and
disease.
 Nurses should be able to identify the Mendelian patterns of inheritance of
genetic conditions in families in the form of a pedigree (family tree)
Educational Role

Impact of Genetic Conditions on
Families

Impact of Genetic Conditions on
Families
 Guilt – Parents with genetic disorder tend to feel guilty, when they come
to know that they might have passed on a condition to a child.
 Depression – When an individual comes to know that he/she has a genetic
condition and the decision not to have a children or decision to terminate a
pregnancy, may result in depression or loss of peace of mind.

REVIEW OF CELLULAR DIVISON :
Meiosis & Mitosis

CELL DIVISION
 Genetic Information is passed from parent to all descendent cells through
cell division namely mitosis.
 There are two cell division –
 Mitosis (Somatic Cell Division)
 Meiosis (Germ cell Division)

CELL CYCLE
 The Cell Cycle is defined as the series of events that take
place in a cell leading to its division and duplication
(replication).
 Major Phases of Cell Cycle
 Cell cycle consists of two major phases namely
 Interphase Phase
 Mitotic Phase

Resting G0 phase
 The term “post-mitotic” is sometimes used to refer to both
quiescent and declining cells. Non proliferative cells in
multicellular eukaryotes generally enter the quiescent G0 state
from G1 and may remain quiescent for long periods of time.

CELL CYCLE
INTERPHASE
 It is the period between successive mitosis of the cell
cycle. The interphase is sub divided in to three phases –
 G1 phase
 S phase
 G2 phase

G1 Phase
 The first phase within interphase, from the end of the previous M
phase until the beginning of DNA synthesis called G1 (G indicating
Gap).
 It is also called the growth phase.
 This phase is marked by synthesis of various enzymes that are
required in S phase, mainly those needed for DNA replication.
 Duration of G1 is highly variable, even among different cells of the
same species.

S PHASE
 The S phase starts when DNA synthesis, when it is complete, all of
the chromosomes have been replicated. E.g. each chromosomes has
two (sister) chromatids
 During this phase, the amount of DNA in the cell has effectively
doubled
 Rate of RNA transcription and protein synthesis are very low during
this phase.

G2 PHASE
 Cell continues to grow and if a problem occurs in DNA replication,
it will be repaired.
 Cell will prepare for mitosis.
 Cell synthesizes proteins needed for cell division

MITOSIS (M Phase)
 Mitosis is the final phase of cell cycle in which two identical (daughter
cells) are produced.
 Mitosis is defined as the process of somatic cell division to form two
identical daughter cells, each with the same chromosomes complement as
the parent cell.
Characteristics features
 It produces two genetically identical “daughter cells” having complete set of
genetic information.
 These daughter cells have exactly the same number of chromosomes (i.e.
46) as the original parent cell.
 The daughter cells are diploid because they contain 46 chromosomes (i.e.
2N= 2 X 23)

MITOSIS (M Phase)
 Estimated (10% of cycle) Includes 2 parts :
1) Mitosis
 Prophase
 Metaphase
 Anaphase
 Telophase
2) Cytokinesis

PROPHASE
 Duration (15 min)
 Chromosomes condense (get thicker) and coil, they
become visible under light microscope.
 The two sister chromatids of each chromosomes attach at
a point called centromere.
 Spindle fibers begin to form from two centrosome, and
they will start moving apart.

METAPHASE
 Duration (20 min)
 Chromosomes reach their most highly condensed state.
 The spindle fibers begin to contract to the centromeres of
the chromosomes, which are now arranged along the
middle of the spindle.

ANAPHASE
 3 Min
 The centromere of each chromosome splits, allowing the
sister chromatids to separate.
 The chromatids are then pulled by the spindle fibers
toward opposite sides of the cell.
 The two sets of chromosomes are identical.

TELOPHASE
 (10 min)
 New nuclear membranes are formed around each of the
two sets of 46 chromosomes.
 The spindle fibers disappear.
 Chromosomes become thinner.
 Cytoplasm starts dividing by contractile ring. At the end,
we will have two diploid daughter cells, which are
identical.

CYTOKINESIS
 The division of the cytoplasm and organelles Begin in anaphase and
completed by the end of telophase .
 This is the last stage of mitosis. It is the process of splitting the
daughter cells apart.
 Each daughter cells contains the same number and same quality of
chromosomes

MEIOSIS
 It is defined as special form of germ cell division that produces
reproductive cells in which each daughter cells receives half the
number of chromosomes i.e. 23
 Site of Meiosis – Occurs in only in germ cell of the gonads
 Sperm in Males
 Ova in females

MEIOSIS STAGES
 Like Mitosis Interphase of the cell cycle includes G1,S,G2 Phases.
Interphase is followed by Meiosis.
 Meiosis consists of two successive stages –
 Meiosis I
 Meiosis II

PHASES OF MEIOSIS I
 PROPHASE I
 METAPHASE I
 ANAPHASE I
 TELOPHASE I

PROPHASE I
 During prophase I, DNA is exchanged between homologous chromosomes
in a process called homologous recombination. This often results in
chromosomal crossover.
 The paired and replicated chromosomes are called bivalents or tetrads.
 The process of pairing the homologous chromosomes is called synopsis.
 At this stage, non-sister chromatids may cross-over at points called
chiasmata

METAPHASE I
 Metaphase 1 is the second phase of Meiosis
 The tetrads from prophase I line up in the middle of the dividing cell
randomly
 Spindle fibers attach to the tetrads from both ends of the cell 24

ANAPHASE I
 Anaphase I begins when the two chromosomes of each bivalent
separate and start moving toward opposite poles of the.
 In anaphase I the sister chromatids remain attached at their
centromeres and move together toward the poles.

TELOPHASE I
 The homologous chromosome pairs reach the poles of the cell.
 The homologous chromosome pairs complete their migration to the
two poles
 A nuclear envelope reforms around each chromosome set, the
spindle disappears, and cytokinesis follows

MEIOSIS II
 The Second division in the meiotic process is termed as equational
division because events in this phase are similar to those of mitosis.
 Meiosis II Differs from mitosis how ?
 Answer - Number of Chromosomes has already been halved in
Meiosis I and the cell does not begin with the same number of
chromosomes as it does in Mitosis

PHASES OF MEIOSIS II
 Mitotic division of 2 haploid cells to produce 4 haploid daughter
cells.
 Prophase -2
 Metaphase -2
 Anaphase 2
 Telophase

Difference Between Mitosis &
Meiosis

NUCLEIC ACIDS
 Nucleic acids are the macromolecules present in all living cell.
 Nucleic Acids are of two types –
 DNA (Deoxyribonucleic Acid)
 RNA (Ribonucleic Acid)

DNA (Deoxyribonucleic Acid)
 James Watson and Francis Crick first proposed the structural model
of DNA in 1953.
 They got the Nobel Prize for their work in 1962.
 Proposed Double Helix model for structure of DNA- remarkable
proposition was base pairing between two strand of polynucleotide.
Comparable to twisted ladder.

NUCLEOTIDES
 Each DNA (and also RNA) strands consists of chain of nucleotides.
 Each nucleotide chain is made up of three main components –
1. Nitrogenous base – These bases are classified into two types –
1. Purines – The purines bases are Adenine (A) and Guanine (G).
2. Pyrimidines – The pyrimidine bases are Thymine (T), Cytosine (C) and
Uracil (U) (Uracil takes place of Thymine in RNA).
2. Deoxyribose Sugar – It is a pentose sugar with 5 carbon atoms
3. Phosphate molecules

BONDS BETWEEN NUCLEOTIDES
 The two nucleotides chain of DNA are held together by two types of molecular
forces.
Hydrogen Bonds
 These are formed between the nitrogenous bases on opposite nucleotide
strands.
 They are always between a purines and pyrimidine nitrogenous base only.
 Adenine base on one strand always pairs with thymine on the other strand (A-
T or T-A)
 Guanine base on one strand pairs with cytosine on the other hand. (G-C or C-
G)
PHOSPHATE DIESTER BONDS
 These bonds are between sugar molecules

CLASSIFICATION OF DNA
 Depending on the types of DNA Sequence
1. Single copy DNA Sequence – In this type nucleotide sequences are
present only once without any repetition of nucleotide. They account
for 50-60 % of human DNA.
2. Moderately repetitive DNA Sequence – In these the nucleotide
sequences are repeated many times and constitute about 25-40 % of
human DNA. Most of them have no function.
3. High repetitive DNA Sequences – It is characterized by repetition of
nucleotides several times (Hundreds to millions). These are non coding
sequences and constitute about 10-15% of Human DNA.

FUNCTION OF DNA
 It is the genetic material, therefore responsible for carrying all the
hereditary information.
 It has property of replication essential for passing genetic information
from one cell to its daughters or from one generation to next.
 Crossing over produces recombination
 Changes in sequence and no. of nucleotides causes Mutation which is
responsible for all variations and formation of new species.
 It controls all the metabolic reaction of cells through RNAs and RNA
directed synthesis of proteins.

GENE
 The gene is the Functional unit of Heredity.
 Each gene is a segment of DNA that give rise to a protein product or RNA.
 A gene may exist in alternative forms called alleles.
 Chromosome in fact carry genes.
 Each chromosome consists of a linear array of genes.

GENE STRUCTURE
 Each gene consist of a specific sequence of nucleotides.
 Gene may be silent or active.
 When active the genes direct the process of protein synthesis.
 Genes do not code for proteins directly but my means of genetic
code.
 The genetic code consists of a sequence codeword called codons.
 A codon for an amino acid consists of a sequence of three
nucleotides base pairs called triplet codon

INITIATOR AND STOP
CODONS
 The boundaries of a gene is known are known as start and stop
codons.
 The start codons tells when to begin protein production and stop
(termination) codons tells when to end the protein production.

CODING REGION
 The nucleotide sequence between the start and stop codons is the
core region known as coding region.
 This region is divided in to two main segment namely exons and
introns.
 Exon – This region codes for producing a protein
 Introns – These are the regions between exons and do not code for a
protein. (Non coding region)

REGULATORY REGION
 These are also non coding regions which control gene expression.
 Promoters – These are the regions which bind to transcription
factors either strongly or weakly.
 Enhancers – These are the regions which can enhance the effect of
weak promoter.
 Silencers – These are the regulatory regions that can inhibit
transcription.

RNA
 The RNA is chiefly presents within the ribosomes and nucleolus.
 RNA differs from DNA in three main ways:
 RNA is single stranded
 The sugar residue within the nucleotide is ribose rather than
Deoxyribose.
 Specific pyrimidine base Uracil is used in place of Thymine.

Types of RNA
 The two major types of RNA are :
 Coding RNA (m-RNA)
 Non Coding RNA (nc-RNA)

m- RNA
 m-RNA contains a coding RNA Sequence. It carries the message
from the DNA to the ribosomes in the cytoplasm required for
protein synthesis.
 It contains both exons and introns similar to DNA.
 During protein synthesis the introns (non coding sequences) are cut
and removed resulting in smaller m-RNA.

NON Coding RNA
 These do not code for proteins.
 Transfer RNA – It conveys the message carried by the m-RNA to
the ribosomes.
 Ribosomal RNA (r-RNA) – They play a significant role in the
binding of m-RNA to ribosomes and protein synthesis.
 Micro-RNA (mi-RNA) – The miRNA play a role in normal
development.

STEPS IN PROTEIN SYNTHESIS
 Several steps are involved in the synthesis of protein.
 The genetic information in cells flows in one way:
 DNA Specifies the synthesis of RNA
 RNA Specifies the synthesis of Amino Acids.
 The two main steps in protein synthesis are transcription and translation.
DNA RNA PROTEIN

TRANSCRIPTION
 Transcription is a process in which genetic information is transmitted from DNA
to RNA .
 It is the first step in protein synthesis and occurs in the nucleus.
 When the genes are active, proteins called transcription factors are produced.
 These transcription factors binds to promoter or enhancer region of genes
 Transfer of the genetic information from DNA –dependent RNA polymerase
(Transcriptase)
 It produces a new complimentary copy of the whole gene and is known as
primary RNA molecule.
 The primary RNA molecule undergoes splicing in which introns are removed
from exons, to produce single-stranded messenger ribonucleic acid (mRNA)
molecule.
 The mRNA migrates from the nucleus to the cytoplasm and is used as a template
for protein synthesis.

TRANSLATION
 Translation is the transmission of the genetic information from mRNA to form
protein.
 In the cytoplasm, mRNA to form protein.
 In the cytoplasm, mRNA attaches to ribosomes, which is the site of protein
production.
 During translation, smaller RNA molecules known as transfer RNA (tRNA) bind
to the ribosome.
 The tRNA deliver amino acid to the ribosomes and synthesizes a linear chain of
amino acids called a polypeptide (primary protein) and later forms proteins.

CHROMOSOMES – SEX DETERMINATION

SEX DETERMINATION
 Sex determination is the process of sex differentiation by which whether a
particular individual will develop into male or female sex.
 The sex chromosomes are responsible for determination of separate
sexes.
 Sex expression is governed by chromosomes and genes.
 In unisexual animals, chromosomes are of two types, autosomes and
allosomes.
 Autosomes – Chromosomes which do not differ in morphology and
number in male and female.
 Allosomes or sex chromosomes – Chromosomes which differ in
morphology and number in male and female and contain genes that
determine sex.

SEX DETERMINATION
 Human body cells have 46 chromosomes arranged in 23 pairs.
 There are 22 pairs of autosomes and one pair of sex chromosomes
(allosomes).
 Female have a perfect pair of sex chromosome XX.
 Male have mismatches pair of sex chromosome XY.
 Both male and female contain equal amount of chromosome 23 pair
 Out of 23 pair: 22 pairs are autosomes 1 pair is sex chromosome.

MENDELLIAN THEORY OF
INHERITENCE

INHERITENCE
 The Law of Inheritance were derived by Austrian Monk named Gregor Mendel.
 He conducted hybridization experiments in garden pea and proposed certain
laws which were known as Mendelian law of Genetics.
 Mendel suggested that the genes occurs in pairs one of which recessive and the
other one is dominant .
 He stated that genes can be paired in three different ways for each trait: AA, aa,
Aa.
 The capital “A” represents the dominant factor and lowercase “a” represents the
recessive
 “Aa will occur roughly twice as often as each of the other two as it can be made
in two different ways “Aa” , “aA”.

INHERITENCE
 Mendelian inheritance is a set of primary statements about the way
certain characteristics (e.g. color of hair, eye, skin etc.) are transmitted
from parent to their offspring.
 Mendel Law’s of Inheritance
 Law of Dominance
 Law of Segregation
 Law of Independent Assortment

LAW OF DOMINANCE
 In heterozygous individual a character is represented by two contrasting
factors called the alleles.
 The one that can express its effect is called as dominant.
 The other allele, which does not show its effect in the heterozygous
individual is called the recessive allele.

LAW OF SEGREGATION
 Mendel stated that the genes normally occurs in pairs in ordinary cells of
the body and each one is derived from each parent.
 During the formation of gametes (sex cells) the two co-existing copies of
a gene separates (segregate) from each other.
 The resultant gamete (sperm or oocyte) receives only one of the two
alleles present in the parent.
 These alleles may behave as dominant or recessive characters.
 The law of segregation states that every individual has two alleles of
each gene and when gametes are produced, each gamete receives one of
these alleles.

LAW OF INDEPENDENT
ASSORTMENT
 Mendel’s second for different law states that genes for different traits-for
example, seed shape and seed color- are inherited independently of each other.
 This conclusion is known as law of independent assortment.
 Genotype RrYy- the alleles R and r will separate from each other as well as
from the alleles Y and y.

ALLELES
 Chromosomes have many genes. Specific genes are located at a specific place
on every chromosomes and this location is known as locus.
 An allele is one of two, or more, forms of a given gene variant.
 Each allele determines a single inherited characteristics in an individual.
 For example – if a gene on a particular chromosomes codes for a characteristics
such as hair color, another gene at the same position on homologous
chromosomes also codes for hair color.
 However these two alleles need not to be identical: one might produce red hair
and the other might produce blonde hair.

TYPES OF ALLELES
 Mono Allelic – Single allele
 Di-Allelic – Two Allele
 Multiple Alleles – E.g. Blood group, hair texture, skin color. Etc.

CATEGORIES OF ALLELES
 Alleles can be categorized as dominant and recessive.
 Dominant alleles are those which is expressed.
 Recessive alleles are those which are unexpressed.
 Co dominant means both alleles of a gene pair exert an observable effect and are
thus equally dominant. (E.g. AB Blood group)

GENOTYPE
 Your genotype is a way of expressing the two alleles that you hold for a
particular gene
 Human eye color is controlled by one gene in particular, for which there are
only 2 available alleles.
B – codes for phenotypically Brown eyes (dominant)
b – codes for phenotypically blue eyes (recessive)
 You need only 1 copy of a dominant allele for it to be expressed
 You need 2 copies of a recessive allele for it to be expressed
BB = Brown eyes
bb = Blue Eyes
Bb =Brown eyes

GENOTYPE
 When one possesses identical alleles on the maternal and paternal
chromosome, this is referred to as a homozygous genotype.
 e.g. BB = homozygous dominant
 e.g. bb = homozygous recessive
 Having two different alleles is a heterozygous genotype.
 E.g. Bb = Heterozygous
 The allele for Brown eyes (B) is dominant
 The allele for Blue eyes (b) is recessive

PHENOTYPE
 The expression of a gene is determined by the combination of dominant
and recessive alleles possessed by the individual.
 Trait that is easily seen (observed trait) is called the phenotype.
 The ABO blood group system represents not only a gene with multiple
alleles, but also a system of codominance.
 Phenotypic expression is not always visible, it can be physical,
biochemical or physiological.

ABO Blood Grouping
 An excellent example of multiple alleles is the ABO Blood Group System
 In ABO there are at least four alleles A1, A2, B and O.
 These alleles control the production of antigens on the surface of red
blood cells.
 An individuals can have any two of these four alleles.
 These two alleles in an individual may be same or different and the blood
group of individual is determined by two of these alleles.
 For example – AA, A1B, OO, A2O.
 The A and B alleles are equally dominant to each other.
 If an individual inherits A allele from one parent and B allele from other
parent, the blood group will be AB.
 The O allele is recessive to both A and B alleles.

ABO Blood Grouping
 If An individual who inherits an A allele from one parent and O allele
from other parent the genotype of AO and the blood group will be A.
 If An individual who inherits an B allele from one parent and O allele
from other parent the genotype of BO and the blood group will be B.
 If An individual who inherits an O allele from one parent and O allele
from other parent the genotype of OO and the blood group will be O.
 A group has two subgroups namely A1 and A2.

MECHANISM OF INHERITENCE
 Mode of inheritance is defined as the manner in which a
particular genetic trait or disorder is passed from one generation
to the next.

Classification of
Genetic Disorder
Single Gene or
Monogenic
Disorders
Autosomal
Dominant
Autosomal
Recessive
X-
linked
Dominant
X-linked
Recessive
Chromosomal
Disorders
Numerical
Aberrations
Structural
Aberrations
Complex/Multifactori
al/Multigenic/Polygen
ic Disorders

Single Gene or Monogenic
Disorders/Mendelian Disorders
 Genetic Disorders that results from mutations in single gene are
called as Single gene or Monogenic Disorders.
 This type of inheritance is called as Mendelian Inheritance.
 Defective gene is responsible for the single gene may be found in
the autosomes or the sex chromosomes.
 When the defective gene is found on an autosome, the mode of
inheritance is said to be of autosomal inheritance
 If it is on the sex chromosomes, it is said to show sex linked
inheritance

Single Gene or Monogenic
Disorders/Mendelian Disorders
 Genes are inherited in pairs-one gene from each parent.
 However, the inheritance may not be equal, and one gene may
overpower the other in their coded characteristic.
 The gene that overshadows the other is called the dominant gene
 The overshadowed gene is the recessive one.
 There are four patterns of Inheritance for Mendelian Disorders
 Autosomal dominant
 Autosomal recessive
 X-linked dominant
 X-linked recessive.

AUTOSOMAL DOMINANT PATTERN OF
INHERITANCE
 Location of mutant gene: These are found on autosomes.
 Required number of defective genes: Only one copy of the mutant
(abnormal) gene is required for effects.
 Autosomal dominant disorder is expressed in heterozygotes (i.e.
one copy of the mutant gene and one copy of normal gene).
 Sex affected: The mutant gene is found on one of the autosomal
chromosomes. Hence, both males and females are equally
affected.

INHERITANCE
 Pattern of inheritance: Every affected individual has an affected
parent.
 Normal members of a family do not transmit the disorder to their
children.
 Risks of transmission to children (offspring): Affected males and
females have an equal risk of passing on the disorder to children.
 When only one parent is affected and other is normal: There is
usually a 50% chance of passing the disease onto children.
 When both parents are affected: There is 75% chance of children
being affected and a 25% chance to be normal

INHERITANCE

AUTOSOMAL RECESSIVE PATTERN OF
INHERITANCE
 Location of mutant gene: These genes are located on autosomes.
 Required number of defective gene: Symptoms of the disease appear only
when an individual has two copies of the mutant gene.
 When an individual has one mutated gene and one normal gene, this
heterozygous state is called as a carrier.
 In the carrier state, the product of the normal gene is able to compensate for the
mutant allele and hence the patients are asymptomatic.
 Pattern of inheritance: For a child to be at risk, both parents must be having at
least one copy of the mutant gene.
 Almost all inborn errors of metabolism are autosomal recessive disorders.
 Sex affected: Females and males are equally affected.

INHERITANCE
 When both parents are heterozygous for the condition: Heterozygous
parents carry one mutated gene and normal gene. When two
heterozygotes mate, 25% of the children will be affected, 50% will be
unaffected heterozygotes and 25% will be normal.

INHERITANCE
 When one parent is affected and the other is normal: All the children
will be unaffected heterozygotes.

INHERITANCE
 When one parent is affected and the other is heterozygote: The
chances are that 50% of children will be unaffected heterozygotes and
50% homozygously affected.

INHERITANCE
 When one parent is normal and the other is heterozygote: This may
result in 50% unaffected heterozygote carriers and 50% normal children.

X LINKED PATTERN OF INHERITANCE
 Almost all sex-linked Mendelian Disorder are X-linked.
 Males with mutations affecting the Y-linked genes are usually infertile.
 Expression of an X-linked disorder is different in males and females. Though
X-linked disorders may be inherited either as dominant or recessive, almost all
X-linked disorders have recessive pattern of inheritance.
 Females: They inherit one X chromosome from each parent (46 XX). The
clinical expression of the X-linked disease in a female is variable, depending on
whether it is dominant or recessive.
 Females are rarely affected by X-linked recessive diseases; however they are
affected by X-linked dominant disease.
 Males: They inherit only one X chromosome from mother and Y chromosome
from father (46 XY). Males have only one X. chromosome and gene mutation
affecting X chromosome is fully expressed even with one copy, regardless of
whether the disorder is dominant or recessive.

X LINKED RECESSIVE TRAIT
 This pattern of Inheritance constitutes a small number of clinical
conditions.
 Location of mutant gene : Mutant gene is on the X chromosomes and
there is no male to male transmission.
 Required number of defective gene: One copy of mutant gene is
required for the manifestation of disease in males, but two copies of the
mutant gene are needed in females.
 Sex affected: Males are more frequently affected than females;
daughters of affected male are all asymptomatic carriers.
 Pattern of inheritance: Transmission is through female carrier
(heterozygous).

Risks of transmission to children (offspring):
 When male is normal and female is a carrier: About 25% of children
may be normal male, 25% normal female, 25% female carrier and 25%
may be male sufferer.

 When male is affected and female is normal: An affected male does
not transmit the disorder to his sons since he donates only a normal Y
chromosome to his son. Thus, all his sons will be normal. An affected
male always donates one copy of his abnormal X-chromosome to all his
daughters and thus all daughters will be asymptomatic carriers.

 When male is affected and female is a carrier: There are chances of
25% of children being female carrier, 25% affected female, 25% normal
male and 25% affected male.

 When male is normal and female is affected: 50% of children will be
female carriers and 50% may be male sufferers

X LINKED DOMINANT DISORDERS
 They are very rare, e.g. vitamin D resistance rickets.
 Location of mutant gene: It is located on the X chromosome and there
is no transmission from affected male to son.
 Required number of defective gene: One copy of mutant gene is
required for its effect.
 Often lethal in males and so may be transmit ted only in the female line.
 Often lethal in affected males and they have affected mothers.
 There is no carrier state. These are more frequent in females than in
males.

 When female is affected and the male is normal: They transmit the
disorder to 50% of their sons and 50% of their daughters.

 When male is affected and the female is normal: They transmit to all
their daughters but none to their sons.

 When both male and female are affected: All the females will be
affected and half of males will be affected

CHROMOSOMAL ABERRATIONS
 Chromosomal aberrations, or abnormalities, are changes to the
structure or number of chromosomes, which are strands of
condensed genetic material.
 Humans typically have 23 pairs of chromosomes, of which 22 pairs are
autosomal, numbered 1 through 22. The last pair of chromosomes are
sex chromosomes, which determine an individual’s sex assignment.
 At birth, most people with XY sex chromosomes are assigned male,
and most individuals with XX are assigned female.
 In general, each parent contributes one set of chromosomes to their
offspring, which collectively make up the 23 pairs of chromosomes.
 A change to any of the chromosomes, in number or structure,
creates a chromosomal aberration and may cause medical
disorders.

CHROMOSOMAL ABERRATIONS
 The chromosomal aberrations/disorders may be broadly classified as
 Numerical chromosomal aberrations
 Structural chromosomal aberrations
 Both may involve either the autosomes or the sex chromosomes.

NUMERICAL CHROMOSOMAL
ABERRATIONS
 Normal cells are diploid containing 46 chromosomes, 22 pairs of
autosomes and 1 pair of sex chromosomes.
 The total number of chromosomes may be either increased or
decreased. The deviation from the normal number of chromosomes is
called as numerical chromosomal aberrations.

TYPES OF NUMERICAL CHROMOSOMAL
ABERRATIONS
NUMERICAL CHROMOSOMES ABERRATIONS
 Aneuploidy
 Monosomy
 Trisomy
 Tetrasomy
 Polyploidy
 Triploidy
 Tetraploidy
 Different Cell Lines: Mosaicism

ANEUPLOIDY
 It is defined as a chromosome number that is not a multiple of 23 (the
normal haploid number). It is caused by either loss or gain of one or
more chromosomes. Aneuploidy may result from nondisjunction or
anaphase lag.
 Trisomy: Numerical abnormalities with the presence of one extra
chromosome are referred to as trisomy. It may involve either sex
chromosomes or autosomes. For examples, patients with Down's
syndrome have three copies of chromosome 21(47 XX, +21), hence
Down's syndrome is often known as trisomy 21. Others are Patau
syndrome (trisomy 13) and Edward's syndrome (trisomy 18).

ANEUPLOIDY
 Monosomy: Numerical abnormalities with the absence or loss of one
chromosome are referred to as monosomy. It may involve autosomes or
sex chromosomes. Monosomy of autosomes is almost incompatible
with survival because of loss of too much genetic information. Example
for monosomy of sex chromosomes is Turner syndrome, in which the
girl is born with only one X-chromosome (45 XO) instead of normal
XX (46 XX).

POLYPLOIDY
 Polyploidy is chromosome number that is a multiple greater than two of
the haploid number (multiples of haploid number 23). Triploidy is three
times the haploid number (69), tetraploidy is four times the haploid
number (92). Polyploidy is incompatible with life and usually results
in spontaneous abortion.

DIFFERENT CELL LINES
 Changes in chromosome number in an individual may not necessarily
be present in all cells but may be found in some cells.
 Mosaicism is defined as the presence of two or more populations of
cells with different chromosomal complement in an individual.
 Mitotic errors during early development. occasionally give rise to
mosaicism. It can involve sex chromosomes or autosomes.

STRUCTURAL CHROMOSOMAL
ABRERRATION
 A second type of chromosomal aberrations is due to alterations in the
structure of one or more chromosomes.
 They may occur either during mitosis or meiosis.
 Structural changes in chromosomes can be balanced or unbalanced.
 Balanced aberration is generally harmless, because there is no loss or
gain of chromosomal material.
 In unbalanced aberrations, chromosomal material is either gained or
lost.

TYPES OF STRUCTURAL CHROMOSOMAL
ABRERRATION
STRUCTURAL CHROMOSOMES ABERRATIONS
 Translocations (exchange)
 Balanced Reciprocal
 Robertsonian Translocation
 Inversions
 Paracentric
 Pericentric
 Isochromosomes
 Deletions (loss)
 Ring Chromosomes
 Insertions

TRANSLOCATION
 It is a structural alteration be tween two chromosomes in which
segment of one chromosome gets detached and is transferred to
another chromosome. There are two types of translocations –
 Balanced reciprocal translocation
 Robertsonian Translocation

Balanced reciprocal translocation
 It is characterized by single breaks in each of two chromosomes
with ex change of genetic material distal to the break. There is no
loss of genetic material.

Robertsonian Translocation
 It is a translocation between two acrocentric chromosomes. The
breaks occur close to the centromeres of each chromosome.
Transfer of the segments leads to one very large chromosome and
one extremely small one.
 The small one is because of fusion of short arms of both
chromosomes which lack a centromere and is lost in subsequent
divisions. This loss is compatible with life.

INVERSION
 It involves two breaks within a single chromosome, the affected
segment inverts with reattachment of the inverted segment. The
genetic material is transferred within the same chromo some.
 There are two types of inversion namely
 Paracentric
 Pericentric.
 Paracentric inversions result from breaks on the same arm (either the
short arm or the long arm) of the chromosome.
 Pericentric inversions results from breaks on the opposite sides of the
centromere where both the short and long arms are involved.

ISOCHROMOSOME
 They are formed due to faulty centromere division.
 Normally, centromeres divide in a plane parallel to long axis of
the chromosome.
 If a centromere divides in a plane transverse to the long axis, it
results in pair of isochromosomes. One pair consists of two short
arms and the other of two long arms.

DELETION
 It is the loss of a part of a chromosome.
 It is of two types namely: interstitial (middle) and terminal (rare).
 Interstitial Deletion - It occurs when there are two breaks within a
chromosome arm. This is followed by loss of the chromosomal material
between the breaks and fusion of the broken ends of the remaining
portion of the chromosome.
 Terminal Deletion - It results from a single break at the terminal part in
a chromosome arm, producing a shortened chromosome bearing a
deletion and a fragment with no centromere. The fragment is then lost
at the next cell division.

RING CHROMOSOME
 It is a special form of deletion. Ring chromosomes are formed by a
break at both the ends of a chromosome.
 There is deletion of the acentric fragments formed due to break and
end-to-end fusion of the remaining centric portion of the chromosome
at the cut ends resulting in a ring chromosome.
 The consequences depend on the amount of genetic material lost due to
the break.
 Loss of significant amount of genetic material will result in phenotypic
abnormalities.

INSERTION
 It is a form of nonreciprocal translocation in which a fragment of
chromosome is transferred and inserted into a nonhomologous
chromosome.
 Two breaks occur in one chromo some which releases a chromosomal
fragment.
 This fragment is inserted into another chromosome following one break
in the receiving chromosome, to insert this fragment.

MUTATIONS
 A mutation is defined as a permanent change in the genetic material
(DNA) which results in a disease. The term mutation was coined by
Muller in 1927.
 Causes
 Spontaneous mutation: Majority of mutations occurs spontaneously due to
errors in DNA replication and repair.
 Induced mutation: Mutations can be caused due to exposure to mutagenic
agents like chemicals, viruses, and ultraviolet or ionizing radiation.
 If the genetic material change/variant does not cause obvious effect
upon phenotype, it is termed as polymorphism. A polymorphism is
defined as genetic variation that exists in population with a frequency
of >1%.

CLASSIFICATION OF MUTATIONS
 Depending on the Cell Involved Mutations are divided into two
types:
 Germ cell mutations: Mutations that affect the germ cells are
transmitted to the progeny/ descendants and can give rise to
inherited diseases.
 Somatic cell mutations: Mutations involving the somatic cells
can produce cancers and some congenital malformations.
These mutations are not inherited and are known as de novo
mutations.

 Depending on the Nature
 Numerical mutation: There is either gain or loss of whole
chromosome (trisomy/monosomy). These usually develop
during gametogenesis and are known as genomic mutations.
 Structural Chromosomal Mutations The rearrangement of
genetic material causes structural change. Structural mutations
may be visible during karyotyping or submicroscopic. The
submicroscopic gene mutations can result in partial or
complete deletion of a gene or more often, a single nucleotide
base.

 Point Mutation - When a nucleotide base is replaced by a
different nucleotide base within a gene, it is known as point
mutation. Majority of point mutation occur in the coding region
of a gene and cause failure of translation and synthesis of the
particular gene product.
 Frame Shift Mutation - This is due to insertion or deletion of
one or more nucleotides. If the number of nucleotide bases
inserted or deleted is not a multiple of 3, the code will be
changed. They are known as frameshift mutation. When deletions
involve a large segment of DNA, the coding region of a gene may
be entirely removed.

 Trinucleotide repeat mutation: The DNA contains several repeat
sequences of three nucleotides (trinucleotide). When they are
repeated directly adjacent to each other (one right after the other),
they are known as tandem repeats. When the repetitive trinucleotide
sequences reach above a particular threshold, they can expand
(amplify) or contract. The amplification is more common. These
trinucleotide-repeat mutation are dynamic (i.e. the degree of
amplification increases during gametogenesis).

MUTATIONS WITHIN NONCODING SEQUENCE
 Transcription of DNA is initiated and regulated by promoter and
enhancer sequences. Point mutations or deletions of these regulatory
regions result in either marked reduction or total lack of
transcription.

DEPENDING ON FUNCTIONAL EFFECT
 Mutations in DNA can lead to either change in the amino acid
sequence of a specific protein or may interfere with its synthesis.
 The consequences vary from those without any functional effect to
those which have serious effects.
 Loss-of-function (LOF) mutations: These mutations cause the
reduction or loss of normal function of a protein. It is usually due to
deletion of the whole gene but may also occur with a nonsense or
frameshift mutation.
 Gain-of-function mutations: These are usually due to missense
mutations. In gain of-function mutation, the protein function is
altered in a manner that results in a change in the original function
of the gene.
 Lethal mutations: These lead to death of the fetus.

Introduction to genetics (Unit - I)for B.Sc. Nursing Students

Introduction to genetics (Unit - I)for B.Sc. Nursing Students

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