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BASIC TERMINOLOGY OF GENETICS

Gene: It is defined as the functional and physical unit of heredity passed from parents to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein.

• Genomics: It is a relatively new term that describes the study of a person’s genes including interactions of those genes with each other and the person’s environment.

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BASIC TERMINOLOGY OF GENETICS

Genetic disorders: It is a disease caused in whole or in part by a ‘variation’ (a different form) or ‘mutation’ (alteration) of a gene.

Alleles: It is a pair of genes that appear at a particular location on a particular chromosome and control the same characteristic, such as blood type or color blindness. Alleles are also called allelomorphs.

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BASIC TERMINOLOGY OF GENETICS

Dominant allele: It is defined as a pair of allele, which is capable to express itself in an allele. For example, TT and Tt both are the genes for tallness, and T is dominant allele, so in both the situations person will be tall.

• Recessive allele: An allele in an organism that does not express itself. For example, one has alleles of eye ‘Bb’ here b is recessive allele therefore person will have brown/blue eye not blue. The effect of recessive allele become known only when it is present in the homozygous state (bb), in this state person will have blue eyes.

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BASIC TERMINOLOGY OF GENETICS

Codominant allele: These alleles express them independently, they do not have any relationship with dominant allele or recessive allele.

• Homozygous allele: It means indistinguishable alleles of single trait. It can be dominant or recessive, i.e., TT and Tt, TT is a homozygous allele.

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BASIC TERMINOLOGY OF GENETICS

Heterozygous allele: It is defined as different alleles on homologous pair of chromosomes, i.e., Rr.

• Mendelian inheritance: Manner in which genes and traits are passed from parents to children. Examples of Mendelian inheritance include autosomal dominant, autosomal recessive, and sex-linked genes.

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BASIC TERMINOLOGY OF GENETICS

Mitochondrial DNA: The genetic material of the mitochondria is the organelle that generate energy for the cell.

• Ribonucleic acid (RNA): A chemical similar to a single strand of DNA. In RNA, the letter U, which stands for uracil, is substituted for T in the genetic code. RNA delivers DNA’s genetic message to the cytoplasm of a cell where proteins are made.

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BASIC TERMINOLOGY OF GENETICS

Genotype: It is defined as the study of the genes and variation therein that a person inherits from his/her parents.

• Phenotype: It is defined as person’s entire physical, biochemical and physiologic make up, as determined by the person’s genotype and environmental factors.

• Karyotyping: It is a picture showing the arrangement of a full set of human chromosomes.

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History of genetics from Darwin to 21st century

Name of the scientist	Year	Contributions
Charles Darwin	1858–1859	The theory of evolution through natural selection and published his work ‘Origin of the Species’.
Gregor Mendel	1866	Publish the results of inheritance of ‘factors’ in pea plants and have discovered the way in which traits are passed from one generation to the next. •• He had also given the law of Independent
Carl Correns, Hugo de Vries and Erich von Tschermak	1900	Rediscovered Mendel’s principles independently

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History of genetics

Walter Sutton and Theodor Boveri	1902	Proposed the chromosomal theory of inheritance
Wilhelm Johannsen	1903	Coined the terms phenotype and Genotype
William Bateson	1905	Coined the term ‘Genetics’.
Nettie Stevens and Edmund Wilson	1905	Independently described the behavior of sex chromosomes X and Y.
Reginald Punnett and William Bateson	1910	Discovered the science of genetic linkage. • They also coined the term ‘epistasis’ to describe the interaction between two different traits.
Oswald Avery	1944	He and his colleagues proved that the DNA is the molecule responsible for inheritance.
James Watson and Francis Crick	1953	He proposed the three dimensional and double helical model of the DNA

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History of genetics

Frederick Sanger	1977	Introduced the process of sequencing the genome of abacteriophage. Later, scientists have done it in other organisms as well.
Kary Mullis	1983 1990	He invented the process called polymerase chain reaction (PCR). In this year, the Human Genome Project was launched.
Ian Wilmut and Keith Campbell	1996 2003 2008	Successfully cloned Dolly the sheep. Dolly was the first mammal to be cloned from an adult cell. Human Genome project was Completed First complete cancer genomes sequenced

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PRACTICAL APPLICATIONS OF GENETICS IN�NURSING

Analyzes the Genetic Basis of Disease and its Reoccurrence
The concept of genotype and phenotype applies to a person’s total genome and their respective traits of

his/her genetic makeup.

Basic mechanism of inheritance and transmission of chromosomes and genes, including the concepts of variation and mutation.
Role of genes and chromosomal mutation and abnormalities in health and illness. For example: Trisomy 21 (Down’s syndrome) or Turner’s syndrome (XO).

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Early Screening and Diagnosis of Genetic�Disorders

Assessment of patient’s health includes obtaining and recording family history information in the form of pedigree.
The format of the pedigree is used to structure and organize data gathered in the assessment process. The pedigree can assist the nurse and genetics specialist to identify possible patterns of inheritance.

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Contd.

The knowledge of the clinical application of modern genetic and genomic technologies enables nurses to inform and support patients and to provide high quality genetics related health care.
Most commonly, genetic screening occurs in prenatal and newborn conditions.

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Genetic screening test

Genetic screening test	Description
Newborn screening	Almost every newborn in the US is screened for several genetic diseases. • Early detection of these diseases, i.e., phenylketonuria and galactosemia) can lead to interventions to prevent the onset of symptoms or minimize disease severity.
Carrier testing	It can be used to help couples to learn if they carry—and thus risk passing to their children—a recessive allele for genetic diseases such as cystic fibrosis, sickle cell anemia, and Tay-Sachs disease. •This type of testing is typically offered to individuals who have a family history of a genetic disorder and to people in ethnic groups with an increased risk of specific genetic conditions.

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Genetic screening test

Genetic screening test	Description
Prenatal diagnostic testing	It is used to detect changes in a fetus’s genes or chromosomes. This type of testing is offered to couples with an increased risk of having a baby with a genetic or chromosomal disorder. • A tissue sample for testing can be obtained through amniocentesis or chorionic villus sampling. • Genetic tests may be used to confirm a diagnosis in a symptomatic individual or used to monitor prognosis of a disease or response to treatment.

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Genetic screening test

Genetic screening test	Description
Predictive or predisposition	Genetic testing can identify individuals at risk of getting a disease prior to the onset of symptoms. •These tests are particularly useful if an individual has a family history of a specific disease and an intervention is available to prevent the onset of disease or minimize disease severity. •Predictive testing can identify mutations that increase a person’s risk of developing disorders with a genetic basis, such as certain types of cancer.

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Clinical Management in Genetic Disorders

These clinical experts can provide detailed information about the disorder, explain inheritance risks, recommend additional testing, develop a treatment plan, and assist in locating a clinical trial.

• The nurse practitioner can then develop a comprehensive evaluation and management plan in collaboration with that genetic specialist.

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Clinical Management in Genetic Disorders

The nurse practitioner also needs to remain knowledgeable about the particular disorder so that when new therapies or treatments (gene therapy) become available, the patient may either be referred back to the genetic professional or the nurse practitioner can engage the patient/family in a dialog about the risks and benefits of the novel therapy.

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Pharmacogenomics

It is concerned with the genetically mediated variation.

The amount of drug metabolizing enzymes are genetically

controlled since the production of these enzymes is genetically controlled.

Example: Primaquine,sulphones and quinolones can cause hemolysis in such people. Nowadays, nurses are in the position to make sure, with the increased translation of pharmacogenomics into clinical practice that adverse drug reactions are avoided and doses are optimized.

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Ethical, Legal, and Social Implications

Beneficence is generally defined as “doing good

to others,”. Beneficence extends to financial and emotional wellbeing, life circumstances, expectations, and personal values.

• Nonmaleficence is defined as “doing no harm,” Nonmaleficence includes the risks associated with

surveillance and prevention strategies as well as

the risks associated with the potential disclosure of

personal medical information if other family members are found to be affected.

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Autonomy: Respecting individual preference, usually through the informed consent process. Anytime a genetic test is offered, individuals should be fully informed about the risks as well as the benefits of genetic testing and should be able to choose or decline testing.
In most cases, patients are asked to make a follow-up appointment to receive their results directly from the nurse practitioner, offering the individual one final opportunity to change their mind by not

returning to get their results.

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Justice: Equal access to genetic services regardless of ethnicity, financial status, or geographic location.

• Privacy: Genetic health information should be

protected from inadvertent disclosure to third parties. Genetic privacy can be a challenge because of the hereditary nature of many disorders that often has implications for other family members.

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Genetic discrimination: Individuals considering genetic testing are often concerned about employment and/or insurance discrimination.

The Genetics information Nondiscrimination Act (GINA), passed in 2008, provides legal protections against genetic discrimination in health insurance and employment in the United States of America.
The Act protects the genetic information of individuals and their family members but does not offer any protections if someone is symptomatic, is being treated for, or has been diagnosed with a genetic condition.
GINA specifically prohibits health insurers from requiring people to provide personal or family genetic information to determine insurance eligibility, coverage, underwriting, or premium-setting decisions.

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Genetic Counseling and Evaluation Services

People seek genetic counseling for various reasons and

at different stages of life. Some are seeking prenatal

information, others are referred after the birth of a child

with a birth defect or suspected genetic condition and

still others are seeking information for themselves or their families because of the presence of, or a family history of, a genetic condition.

Regardless of the timing or setting, genetic counseling is offered to all people who have questions about genetics and genomics and their health.

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Nursing Implication

Nowaday, nurses are in an ideal position to assess thepatient's health, genetics and family history and to make referrals for specialized diagnosis and treatment.
�� They offer anticipatory guidance by explaining the purpose and goals of a referral.
�� They collaborate with other health care providers in giving supportive and follow-up counseling and coordination follow-up and case management.

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IMPACT OF GENETICS ON FAMILIES

Impact of Genetics in families

Patients

Parents

Family

Communities

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Patients�

A genetic diagnosis may lead to negative reactions in a person who suffered from various genetic disorders.
Patients identified with a mutation may consider themselves at fault or ‘broken’ or interpret their diagnoses as leading to something they cannot fight.
The reaction to a diagnosis varies from individual to individual and is affected by many factors including gender, education, and religious and cultural beliefs.
By being aware of these differences and understanding patients’ backgrounds, a genetic nurse should be able to communicate with patients effectively.

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Parents

The diagnosis of a genetic condition may put stress on a relationship. For adult-onset diseases, unaffected spouses may view their partners differently, and the diagnosis can lead to a breakdown in communication.
Couples with an affected child often face difficult family planning decisions because future children may be at higher risk.
Parents may also be faced with hard choices regarding

prenatal testing and termination of pregnancy.

The magnitude of these decisions and their outcomes has an impact on the individuals involved and on their relationship.

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Family

Unaffected family members should not be forgotten n the case of a genetic disorder. When one family member is diagnosed with a mutation, family members who do not have the mutation often feel guilty that loved ones are affected when they are not.
Siblings of children with special needs sometimes

feel neglected because parents need to focus more

time and effort on their siblings.

Including unaffected family members in the planning of care for individuals with special needs can help them come to grips with their own emotional issues.

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Family

Adults who are diagnosed with a genetic condition and are considering having a child will need to consider the risk of having an affected child as well as their ability to care for the child.

• In cases in which a genetic test is predictive, other family members may misinterpret the results as a diagnosis rather than an indicator of risk for a condition.

In some cases, a genetic test may reveal the risk status of other family members, who may not wish to know this information, potentially encroaching upon their

autonomy or privacy.

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Family

The financial burden of a chronic genetic condition can also lead to stress among family members. A family already struggling financially may be intimidated by the costs associated with caring for a child with special needs.

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Communities

Genetic testing can also affect the community at large. Genetics has been used in the past to stigmatize and discriminate along ethnic or racial lines, and underserved or underrepresented communities often view genetic research and services with distrust.
They may feel that the results of a genetic test or newborn screening will be used to segregate their communities.

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OVERVIEW OF CELL DIVISION

Mitosis and meiosis are two distinctly different types of cell division. As the cell division is the part of the cell cycle; where cell grow and divide. Therefore, it is wise to first understand about the cell cycle.
Cells with nuclei have 46 chromosomes and divide

by mitosis, a process that results in two new, genetically identical daughter cells. The only exception to this is the formation of gametes (sex cells), i.e., ova and spermatozoa, which takes by meiosis.

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OVERVIEW OF CELL DIVISION

The period between two cell divisions is known as the cell cycle. This has two phases that can be seen on light microscopy: mitosis (M phase and interphase).

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Interphase

This is the longer phase and three separate stages are

recognized:

1. First gap phase (G1): The cell grows in size and volume. This is usually the longest phase and most variable in length. Sometimes cells do not continue to go round the cell cycle but entering a resting phase(G0); despite being called the resting phase, cells at this stage are usually highly active, carrying out their specific functions. The cell may stay in G0 for the rest of its life, but may also re-enter the cell cycle and start

dividing again if need be.

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Interphase

2. Synthesis of DNA (S phase): The chromosome replicate, forming two identical copies of DNA. Therefore, following the S phase, the cell now has 92 chromosomes, i.e., enough DNA for two cells, and is nearly ready to divide by mitosis.

3. Second gap phase (G2): There is further growth and preparation for cell division.

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Mitosis

Mitosis is a continuous process involving four distinct stages visible by light microscopy
Prophase
Metaphase
Anaphase
Telophase

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Steps of mitotic division

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Meiosis I

Meiosis is preceded by an interphase consisting of three

stages.

The G1 phase (also called the first gap phase) initiates this stage and is focused on cell growth.
The S phase is next, during which the DNA of the chromosomes is replicated. This replication produces two identical copies, called sister chromatids, that are held together at the centromere by cohesion proteins. The centrosomes, which are the structures that organize the microtubules of the meiotic spindle, also replicat
Finally, during the G2 phase (also called the second gap phase), the cell undergoes the final preparations for meiosis.

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Prophase I

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Five distinct sub-stages of prophase

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Prometaphase I

The key event in prometaphase I is the formation of the spindle fiber apparatus where spindle fiber microtubules attach to the kinetochore proteins at the centromeres.
Microtubules grow from centrosomes placed at opposite poles of the cell. The microtubules move toward the middle of the cell and attach to one of the two fused homologous chromosomes at the kinetochores.
At the end of prometaphase I, each tetrad is attached to

microtubules from both poles, with one homologous

chromosome facing each pole. In addition, the nuclearmembrane has broken down entirely.

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Metaphase I

During metaphase I, the tetrads move to the metaphase plate with kinetochores facing opposite poles. The homologous pairs orient themselves randomly at the equator.

• In each cell that undergoes meiosis, the arrangement of the tetrads is different.

• The number of variation is dependent on the number of chromosomes making up a set. There are two possibilities for orientation at the metaphase plate. The possible number of alignments, therefore, equals 2n, where n is the number of chromosomes per set.

• Given these two mechanisms, it is highly unlikely that any two haploid cells resulting from meiosis will have the same genetic composition.

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Chromosomes arrangements of metaphase I

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Anaphase I�

In anaphase I, the microtubules pull the attached chromosomes apart. The sister chromatids remain tightly bound together at the centromere. The chiasmata are broken in anaphase I as the microtubules attached to the fused kinetochores pull the homologous chromosomes apart.

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Telophase I and Cytokinesis

In telophase I, the separated chromosomes arrive at opposite poles. In some organisms, the chromosomes decondense and nuclear envelopes form around the chromatids in telophase I.
Then cytokinesis, the physical separation of the cytoplasmic components into two daughter cells, occurs without reformation of the nuclei. In nearly all species of animals and some fungi, cytokinesis separates the cell contents via a cleavage furrow (constriction of the actin ring that leads to cytoplasmic

division).

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In plants, a cell plate is formed during cell cytokinesis by Golgi vesicles fusing at the metaphase plate. This cell plate will ultimately lead to the formation of cell walls that separate the two daughter cells.

• Two haploid cells are the end result of the first meiotic division. The cells are haploid because at each pole there is just one of each pair of the homologous

chromosomes. Therefore, only one full set of the chromosomes is present. Although there is only one

chromosome set, each homolog still consists of two sister chromatids.

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Meiosis II

During meiosis II, the sister chromatids within the two

daughter cells separate, forming four new haploid gametes.

Meiosis II initiates immediately after cytokinesis,

usually before the chromosomes have fully decondensed.

The two cells produced in meiosis I go through the events of meiosis II together. During meiosis II, the sister chromatids within the two daughter cells separate, forming four new haploid gametes. The mechanics of meiosis II is similar to mitosis, except that each dividing cell has only one set of homologous chromosomes.

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Differentiation of prometaphase I and anaphase I in the meiosis I and meiosis II

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Prophase II

If the chromosomes decondensed in telophase I, they condense again. If nuclear envelopes were formed, they fragment into vesicles. The centrosomes that were duplicated during interphase I move away from each other

toward opposite poles and new spindles are formed.

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Prometaphase II

The nuclear envelopes are completely broken down and the spindle is fully formed. Each sister chromatid forms an individual kinetochore that attaches to microtubules from opposite poles.

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Metaphase II

The sister chromatids are maximally condensed and aligned at the equator of the cell.

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Anaphase II

The sister chromatids are pulled apart by the kinetochore microtubules and move toward opposite poles. Nonkinetochore microtubules elongate the cell.

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Telophase II and Cytokinesis

The chromosomes arrive at opposite poles and begin to decondense. Nuclear envelopes form around the chromosomes.
Cytokinesis separates the two cells into four unique haploid cells. At this point, the newly-formed nuclei are both haploid.

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Telophase II and Cytokinesis

The cells produced are genetically unique because of the random assortment of paternal and maternal homologs and because of the recombining of maternal and paternal segments of chromosomes (with their sets of genes) that occurs during crossover.

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Comparison of Meiosis and Mitosis

	Mitosis	Meiosis
Purpose	Cell regeneration, growth, and asexual reproduction.	The production of gametes for sexual reproduction.
Number of divisions	Consist of single nuclear division that results in two nuclei that are usually partitioned into two new daughter cells. They are genetically identical to the original nucleus.Consist of two nuclear divisions resulting in four nuclei that are usually partitioned into four new haploid daughter cells. Nature of genetic material	Consist of two nuclear divisions resulting in four nuclei that are usually partitioned into four new haploid daughter cells.

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Comparison of Meiosis and Mitosis

	Mitosis	Meiosis
Nature of genetic material	They have the same number of sets of chromosomes, one set in the case of haploid cells and two sets in the case of diploid cells.	The nuclei resulting from meiosis are not genetically identical and they contain one chromosome set only. This is half the number of chromosome sets in the original cell, which is diploid.

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Meiosis II resembles a normal mitosis

as contrast to meiosis I. In some species, cells enter a brief interphase, or interkinesis, before entering meiosis II. Interkinesis lacks an S phase, so chromosomes are not duplicated.

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CHARACTERISTICS AND STRUCTURE OF�GENES

Genes are the functional unit of heredity, variation,

mutation and evolution. Genes determine the physical

as well as physiological characteristics of organisms.

Genes are responsible for transferring these characters from parents to the offspring generation after generation.

• They are situated in chromosomes.

• Every gene occupies a fixed position in a chromosome.

This position is called a locus.

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They are arranged in a single linear order in a

chromosome as beads on a string.

They express them by the synthesis of proteins and enzymes, which control cell metabolism.
They determine the physical and metabolic characteristics of the cell. Each gene synthesizes a particular protein which acts as an enzyme and brings about the appropriate change.

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Molecular Concept of Genes

A gene is composed of a segment of DNA except in some viruses, which have genes consisting of a closely related compound called RNA.

•A DNA molecule is composed of two chains of

nucleotides that wind about each other to resemble a

twisted ladder.

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The sides of the ladder are made up of sugars and

phosphates, and the rungs are formed by bonded

pairs of nitrogenous bases.

• These bases are adenine (A), guanine (G), cytosine (C), and thymine (T).

• An A on one chain bonds to a T on the other chain

(thus forming an A–T ladder rung); similarly, a C on

one chain bonds to a G on the other.

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If the bonds between the bases are broken, the two

chains unwind, and free nucleotides within the cell

attach themselves to the exposed bases of the now separated chains.

•• The free nucleotides line up along each chain

according to the base-pairing rule—A bonds to T, C

bonds to G.

•• This process results in the creation of two identical

DNA molecules from one original and is the method

by which hereditary information is passed from one

generation of cells to the next generation.

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Gene Expression

Gene expression is the process by which the genetic code—the nucleotide sequence—of a gene is used to direct protein synthesis and produce the structure of the cell.

Genes that code for amino acid sequences are known as ‘structural genes’.

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Gene Expression

1. Transcription: The production of messenger RNA

(mRNA) by the enzyme RNA polymerase, and the

processing of the resulting mRNA molecule.

2. Translation: It is the use of mRNA to direct protein synthesis, and the subsequent post-translational processing of the protein molecule

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Structure of gene

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Exons: Exons code for amino acids and collectively determine the amino acid sequence of the protein product. It is these portions of the gene that are represented in final mature mRNA molecule.
Introns: Introns are portions of the gene that do not code for amino acids, and are removed (spliced) from the mRNA molecule before translation.

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Transcription

Transcription involves four steps:
Initiation
Elongation
Termination
Processing

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Translation

Translation involves four steps:
Initiation
Elongation
Termination
Pos- translation processing of the protein

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Gene Regulation

Gene regulation is a label for the cellular processes that control the rate and manner of gene expression.

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Mechanisms of gene regulation

Regulating the rate of transcription. This is the most economical method of regulation.
Regulating the processing of RNA molecules, including alternative splicing to produce more than one protein product from a single gene.
Regulating the stability of mRNA molecules.
Regulating the rate of translation.

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CHROMOSOME

Chromosomes are organized structures of DNA and proteins that are found in cells.
A chromosome is a singular piece of DNA, which contains many genes, regulatory elements and other nucleotide sequences.
Chromosomes also contain DNA-bound proteins, which serve to package the DNA and control its functions.

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The normal chromosomal complement in a male is 46, XY and in a female 46, XX.
Any deviation either in number or structure of the chromosomes is referred to as chromosomal aberration.

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Chromosomal Disorders due to Numerical�Abnormalities

Aneuploidy: It refers to loss or gain of a chromosome. Aneuploidy can be due to nondisjunction of autosomes, i.e., chromosomes 1–22 or sex chromosomes
Trisomy: The cell has one extra chromosome

(2n+1).

� Monosomy: The cell has one chromosome less (2n–1).

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Chromosomal disorders due to aneuploidy

Genetic disorder	Defect in	Genotype
Down syndrome	Autosomes	Trisomy of 21st chromosome
Patau syndrome	Autosomes	Trisomy of 13th chromosome
Edwards‘ syndrome	Autosomes	Trisomy of 18th chromosome
Klinefelter syndrome	Sex chromosome	XXY
Turner syndrome	Sex chromosome	Monosomy- XO
Triple X syndrome	Sex chromosome	XXX
XYY syndrome	Sex chromosome	XYY

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Euploidy: Loss or gain of the whole set of chromosome. Mostly occurs in plants.
�Haploid: Loss of one set of the chromosomes, i.e., ‘n’ number of chromosomes.
Polyploid: Addition of one or more set of

chromosomes, e.g., ‘3n (triploid)’, ‘6n (hexaploid)’ etc.

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Chromosomal Disorders due to Structural�Abnormalities

Deletion

A portion of the chromosome is lost during cell division.

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CONTD.

Duplication

The presence of part of a chromosome in excess is known as duplication

Example of disorder due to duplication

Fragile X: Affects 1:1500 males and 1:2500 females. This is the most common form of mental retardation, where the CGS segment is repeated more than 200 times.

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Inversion

Inversion results from breakage and reunion of a part of the chromosome rotating by 180° on its own axis. So there occurs a rearrangement of genes. Its effects are not as

severe as in other structural defects

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Translocation

The shifting or transfer of a set of genes or part of a chromosome to a nonhomologous one is known as translocation.
There is no addition or loss of genes, only the rearrangement occurs

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MENDELIAN THEORY OF INHERITANCE

First Law: Law of Dominance

When individuals with one or more sets of contrasting characters (now known as phenotypes) are crossed, then the characters that appear in F1 generation are called dominant characters, and the characters that remain hidden are called recessive characters.

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Second Law: Law of Segregation

This law is also referred to as law of purity of gametes. During the formation of male and female gametes, (generally sperm and ova in animals or pollen grains and in ovule of plants), factors (alleles) responsible for a particular character separate and are passed into different gametes. This process implies that the gametes are either pure for dominant alleles or for recessive.

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These gametes can unite randomly in different possible combinations during fertilization and produce the genotype for the traits of the progenies. In a zygote, the two members of an allele pair remain together without being contaminated. This is known as law of segregation.

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Third Law: Law of Independent Assortment

This law is also known as inheritance law and is defined as alleles of different genes, which distribute independently of one another during gamete formation.

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Diseases related to inheritance pattern

Inheritance pattern	Characteristics	Disease examples
Autosomal dominant	Each affected person usually has an affected parent; occurs in every generation.	Huntington’s disease neurofibromatosis, achondroplasia, familial hypercholesterolemia.
Autosomal recessive	Both parents of an affected person are carriers; not typically seen in every generation.	Tay-Sachs disease, sickle cell anemia, cystic fibrosis, phenylketonuria (PKU).

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Autosomal dominance inheritance

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Autosomal recessive inheritance

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Inheritance pattern	Characteristics	Disease examples
X-linked dominant	Females are more frequently affected because all daughters and no sons of an affected man will be affected; can have affected males and females in same generation if the mother is affected.	Hypophosphatemic rickets (vitamin D-resistant rickets), ornithine transcarbamylase deficiency.
X-linked recessive	Males are more frequently affected; affected males often present in each generation.	Hemophilia A, Duchenne muscular dystrophy.

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X-linked dominant and recessive inheritance

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Inheritance pattern	Characteristics	Disease examples
Mitochondrial inheritance	Can affect both males and females, but only passed on by females because all mitochondria of all children come from the mother; can appear inevery generation.	Leber’s hereditary, optic neuropathy, Kearns-Sayre syndrome.

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Mitochondrial inheritance

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MULTIPLE ALLELES AND BLOOD GROUPS

The term ‘blood group’ refers to the entire blood group system comprising red blood cell (RBC) antigens whose specificity is controlled by a series of genes, which can be allelic or linked very closely on the same chromosome.
‘Blood type’ refers to a specific pattern of reaction to testing antisera within a given system.

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ABO System

ABO remains the most important in transfusion and transplantation since any person above the age of 6 months possess clinically significant anti-A and/or anti-B antibodies in their serum.
Blood group A contains antibody against blood group B in serum and vice-versa, while blood group O contains no A/B antigen but both their antibodies in serum.

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ABO Phenotypes

The four basic ABO phenotypes are O, A, B, and AB.
The blood group was divided into two phenotypes, A1 and A2.
RBCs with the A1 phenotype react with anti-A1and make up about 80% of blood type A.
RBCs with the A2 phenotype do not react

with anti-A1 and they make up about 20% of blood type A.

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The immune system forms antibodies against

whichever ABO blood group antigens are not found on

the individual’s RBCs.

a group A individual will have anti-B antibodies and a group B individual will have anti-A antibodies. Blood group O is common, and individuals with this blood type will have both anti-A and anti-B in their serum.
Blood group AB is the least common, and these individuals will have neither anti-A nor anti-B in

their serum .

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ABO blood groups and red cell antigens

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Rhesus System

Rhesus-system is the second most important blood group system after ABO. Currently, the Rh-system consists of 50 defined blood group antigens out of which only five are important.
RBC surface of an individual may or may not

have an Rh factor or immunogenic D-antigen.

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The status is indicated as either Rh positive (D-antigen present) or Rh-negative (D-antigen absent).
In contrast to the ABO system, anti-Rh antibodies

are, normally, not present in the blood of individuals with

D-negative RBCs, unless the circulatory system of these

individuals has been exposed to D-positive RBCs.

These immune antibodies are immunoglobulin G (IgG) in nature and hence, can cross the placenta. Prophylaxis is given against Rh immunization using anti-D Ig for pregnant

Rh-negative mothers who have given birth to Rh-positive

child

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GENE MUTATION (ERROR IN TRANSMISSION)

If heritable change occurs in the structure of a gene then it is called as gene mutation or point mutation.
When change occurs is chromosomes (structural or numerical) then it is referred as chromosomal mutation.

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GENE MUTATION (ERROR IN TRANSMISSION)

Mutations can lead to changes in the structure of an encoded protein or to a decrease or complete loss in its expression. Because a change in the DNA sequence affects all copies of the encoded protein,

mutations can be particularly damaging to a cell or organism.

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Genotype- the entire set of genes carried by an individual is called its genotype.
Phenotype-the function and physical appearance of an individual is referred to as its phenotype.

Genotype usually denotes whether an individual carries mutations in a single gene (or a small number of genes), and phenotype denotes the physical and functional consequences of that genotype.

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Somatic and Germinal Mutation

If the mutation occurs in somatic cell then is called somatic mutation

and

if it occur in germ cell (egg or sperm) it is known as germinal mutation.
The somatic mutation cannot be transmitted to

offspring while germinal mutation occurs in germ cell hence is transmitted to next generation.

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Somatic mutation produces local phenotypical

change in that individual while germinal mutation will show generalized effect on that individual.

Individuals with somatic mutation are mosaics (they will have genetically two different types).
In case of germinal mutation, as mutation is transmitted through a sperm or egg, the resulting offspring will not be mosaic because all its cells will carry the mutation.

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Molecular Basis of Gene Mutation (Point Mutation)

Through the process of replication of DNA is very accurate but, sometimes alteration may take place in the arrangement of nucleotides in a polynucleotide chain of DNA molecule.
These smallest changes may involve the addition, deletion or substation of a single nucleotide pair in the DNA molecule.

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Substitution Mutation

This is a relatively common kind of mutation. In this kind of mutation one nitrogenous base of triplet code of DNA is replaced by another nitrogenous base.
This changes the codon, which may codes for different amino acid.

-Example ---- if in GAG triplet code of mRNA (which codes for glutamic acid) base A is replaced by U, at thtime of transcription, then code GUG will produce valine amino acid instead of glutamic acid. This one different amino acid in a polypeptide chain will lead to formation of altered protein whose effect may be seen as many abnormalities throughout the body.