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Concepts and importance of genetics

Ashly Elizabeth Emmanuel

Branch of biological sciences which deals with the transmission of characteristics from parent to offspring.

The term genetics was coined by BATESON in 1906. It has been derived from the greek word gene (to become)

Heredity-: study of factors responsible for the resemblance between parents and their offsprings Variation-: concerned with the forces or influences due to which no two organisms are exactly alike.

In the nucleus of each cell, the DNA molecule is packaged into thread-like structures called chromosomes

Each chromosome has a constriction point called the centromere, which divides the chromosome into two sections, or arms. The short arm of the chromosome is labeled the p arm. The long arm of the chromosome is labeled the q arm. The location of the centromere on each chromosome gives the chromosome its characteristic shape, and can be used to help describe the location of specific genes.

Genes are the basic unit of heredity that determine the unique physical, chemical and mental characteristics and traits of all individuals

Deoxyribonucleic acid or DNA, is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms

The information in DNA is stored as a code made up of four chemical bases: adenine (A), guanine (G), cytosine (C), and thymine (T). DNA bases pair up with each other, A with T and C with G, to form units called base pairs. Each base is also attached to a sugar molecule and a phosphate molecule.

Together, a base, sugar, and phosphate are called a nucleotide. Nucleotides are arranged in two long strands that form a spiral called a double helix.

Knowledge of genetics is helpful in understanding the causation of diseases Help us to understand how normal variations between individuals are brought about

Helpful in preventing genetic disorders through genetic counseling and antenatal diagnosis. Helps to solve legal problems.

Genetic testing in Neonates & Children

The analysis of human DNA in any of its forms or related products (chromosomes, RNA, proteins)
Genetic Testing (also called DNA-based tests) is used to test for genetic disorders which involves direct examination of the DNA molecule itself.

Uses of Genetic Testing:

To detect disease-related genotypes, mutations, phenotypes, or karyotypes for clinical purposes

More definitions
Genotype vs. Phenotype
The genetic make-up, as distinguished from the physical appearance

A genetic change, usually one that is associated with a disease

A visual presentation of chromosomes

Two Main Types of Genetic Tests

1. Constitutional
Tests for mutations that affect ALL CELLS in the body, and have been there since conception

2. Acquired
Tests for changes that affect only certain cells or cell types in the body, and that occurred later in life

Genetic Tests for Constitutional Mutations

Molecular Tests Cytogenetic Tests Biochemical Tests

Molecular Test: Example

Analysis of DNA sequence in patient with a rare inherited disease
Muscular Dystrophy Gene: DMD Clinical Picture
1 in 3500 male births progressive muscle weakness starting in early childhood wheelchair by age 12 death in 20s

Molecular Test: Muscular Dystrophy

Obtain blood sample from child Read the DNA sequence of the DMD gene Identify the mutation that caused the disease

How is this information useful?

Can test Mother Is she an unaffected carrier of the mutation? Is she at risk to have more children with this disease? Can test siblings of affected child Can offer prenatal diagnosis in Mothers next pregnancy OR Can offer pre-implantation genetic diagnosis Can provide information about prognosis

Cytogenetic Test: Example

Karyotype to examine the chromosomal complement of an individual including number, form, and size of the chromosomes. Frequently used for children who present with multiple anomalies, developmental delay, autism

Cytogenetic Test: Child with autism

Obtain a blood sample from baby Look at chromosomes

How is this information useful?

Can determine exactly which genes are involved Can test parents and siblings of affected child to see if they carry the abnormality Can offer prenatal diagnosis in next pregnancy OR Can offer pre-implantation genetic diagnosis Can provide information about prognosis

Biochemical Test
Analyzes the quantity of a downstream product of a gene (e.g. not looking directly at the gene, or the chromosome). Example: Newborn Screening

Biochemical Test: PKU

Phenylketonuria Inherited metabolic disorder If untreated, leads to mental retardation, seizures Affects 1 in 20,000 newborns
Missing enzyme: Phenylalanine Hydroxylase Measure amount of Phenylalanine in babys blood

How is this information useful?

Can diagnose the baby in time to treat and avoid all clinical consequences of the disease
Treatment: Restrict phenylalanine in the diet

Can test siblings of affected child to see if they are carriers for the disease (1 in 70 in the general population are carriers)

Genetic Tests for Acquired Mutations

Molecular Tests Cytogenetic Tests

Tests for changes that affect only certain cells or cell types in the body, and that occurred later in life

Molecular Test for Acquired Disease

KRAS gene test on tumor tissue from patients with colorectal cancer
Obtain tumor from patient Extract DNA; treat with enzyme that allows visualization of the mutation

How is this information useful?

Patients whos colon tumors do not have a KRAS mutation are much more likely to respond to Cetuximab therapy Identifies patients most likely to benefit from specific therapies Allows choice of alternative therapies (and saves time and money) for patients unlikely to respond

Cytogenetic Test for Acquired Disease: Example

Her-2/neu gene amplification in Breast Cancer
Occurs early in oncogenesis Seen in up to 1/3 of breast cancers Associated with poor prognosis Responds to Herceptin (trastuzumab) treatment Does not respond to Tamoxifen treatment

How is this information useful?

Assists in selection of patients for chemotherapy, and which therapy to use Predicts response to adjuvant therapy Increases survival Allows choice of alternative therapies (and saves time and money) for patients unlikely to respond

Genetic Testing for Specific Conditions

1. Take a sample (blood/amniotic fluid, mouth swab) 2. Use staining of chromosomes to locate any chromosome abnormalities
3. or use matching DNA sequences or antibodies to detect gene abnormalities

Genetic testing in neonates

Performed to diagnose a disorder or screen for a potential pathologic condition. It can be done by testing newborn blood sample Eg: diagnosis of PKU, Galactosemia, trysomy etc...

Neural tube defects

Eg: spina bifida occulta: (multifactorialdeficiency of follic acid in maternal diet, positive family history etc..) Screening tests: maternal serum AFP, ultrasound, CT

Errors in metabolism
PKU : blood and urine tests Congenital hypothyroidism : Neonatal Screening for T4 (thyroxine), TSH or both

Screeing of urine or serum for galactose

Cystic fibrosis
Testing for high sweat chloride level

Trisomies 13, 18 & 21

Amniocentesis Chorionic villi sampling USG Karyotyping


Category 1: disorders requiring immediate treatment/prevention/surveillance Phenylketonuria-: dietary management Multiple endocrine neoplasms -:life preserving thyroidectomies

Category II
Testing assymptomatic carrier to define reproductive risks-for future Sex linked disorders- hemophilia, muscular dystrophy Autosomal recessive disorders-cystic fibrosis, sickle cell diseases

Category III
Testing healthy young person with predisposition to develop disease Familial breast cancer Hereditary non polyposis colon cancer-: avoid environmental dietary factors

Category IV
Testing healthy young person who will develop disease Polycystic kidney diseases Parkinsons disease

Ethical concerns
Confidentiality should be maintained

Nursing aspects
Assist with testing procedures Support the client and family Appropriate education and clarification Support for the family who chooses therapeutic abortion, before, during & after procedure

Should be able to explain the complete genetic information to the family in a simple way Must take a thorough family history, informations about exposure and life style Information about the affected and unaffected conditions

Constitutional genetic tests impact patients with inherited disorders and their families, by providing information about diagnosis, prognosis, treatment, and informing reproductive decisions Genetic tests for acquired diseases impact patients with diseases like cancer, provide information about diagnosis and prognosis, and inform treatment decisions Genetics and genetic testing impacts many phases of our lives, and will do so even more in the future