Concept and basics of genetics

Concept and Basics of Genetics

& Practical application in

Nursing

Genetics

• The process of transmission of characters from one generation to next generation is called the inheritance or heredity.

Branches of Genetics

1. Cytogenetics2. Molecular genetics3. Biochemical genetics4. Cancer genetics5. Immunogenetics6. Developmental genetics7. Behavioral genetics8. Population genetics

Importance of genetics in Medicine

• ≈50% of first trimester abortion are due to chromosomal abnormalities

• Congenital malformation: ≈2-3% of newborns.• 2% infants are born with single gene disorder• More than half of childhood blindness,

deafness and mental retardation are due to genetic disorders.

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Genetic Information• Gene – basic unit of genetic

information. Genes determine the inherited characters.

• Genome – the collection of genetic information.

• Chromosomes – storage units of genes.

• DNA - is a nucleic acid that contains the genetic instructions specifying the biological development of all cellular forms of life

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Chromosome Logical Structure

• Locus – location of a gene/marker on the chromosome.

• Allele – one variant form of a gene/marker at a particular locus.

Locus1Possible Alleles: A1,A2

Locus2Possible Alleles: B1,B2,B3

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Human Genome

Most human cells contain 46 chromosomes:

• 2 sex chromosomes (X,Y):XY – in males.XX – in females.

• 22 pairs of chromosomes named autosomes.

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Genotypes Phenotypes

• At each locus (except for sex chromosomes) there are 2 genes. These constitute the individual’s genotype at the locus.

• The expression of a genotype is termed a phenotype. For example, hair color, weight, or the presence or absence of a disease.

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Genotypes Phenotypes (example)

• Eb- dominant allele.• Ew- recessive allele.

genotypes

phenotypes

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Dominant vs. Recessive A dominant allele is expressed even if it is paired with a recessive allele.

A recessive allele is only visible when paired with another recessive allele.

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Two members of a gene pair segregate from each other into the gametes, so half the gametes carry one member of the pair and the other half carry the other member of the pair.

Mendel’s 1st Law

Y / y y / y

½y/y

½Y/y

½y

½Y

all yGamete production

Gamete production

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Mendel’s 2nd Law• Different gene pairs assort independently

in gamete formation.

Gene pairs on SEPARATE CHROMOSOMES assort independently at meiosis.

This “law” is true only in some cases.

DNA

• 1953 - James Watson, Francis Crick, Rosalind Franklin & Maurice Wilkins

• Lead to understanding of mutation and relationship between DNA and proteins at a molecular level

• 1959 – “Central Dogma”– DNARNAprotein

Genetic Concepts

• Chromosome – – double stranded DNA

molecule packaged by histone & scaffold proteins

DNA double helix

nucleosome

30nm fiber

condensed chromosome

Genetic Concepts

• Chromosome numbers– Constant for an organism– n - haploid number – 2n – diploid number

• Karyotype

Genetic Concepts

Y

Genetic Concepts

• Chromosome numbersEach individual inherits 23 chromosomes from

father and 23 from mother.Humans: 2n= 46 chromosomesHumans 23 paternal, 23 maternalHumans n = ____Each maternal & paternal pair represent

homologous chromosomes - called homologs

Genetic Concepts

(a) Chromosomal composition found in most female human cells (46 chromosomes)

(b) Chromosomal composition found in a human gamete (23 chromosomes)

1 2 3 4 5 6 7

XX

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9 10 11 12 13 14 15

17 18 19 20 21 22

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1 2 3 4 5 6 7

X

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9 10 11 12 13 14 15

17 18 19 20 21 22

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Diploid Haploid

Genetic Concepts• Homologous Chromosomes– Share centromere position– Share overall size– Contain identical gene sets at matching positions (loci)

gene for color

gene for shape

Genetic Concepts• Gene – sequence of DNA which is transcribed

into RNA – rRNA, tRNA or mRNA

• Locus – the position on a chromosome of a particular DNA sequence (gene)

G Locus – gene for color

W Locus – gene for shape

Genetic Concepts• DNA is mutable• A variation in DNA sequence at a locus is

called an allele– Diploid organisms contain 2 alleles of each locus

(gene)• Alleles can be identical – homozygous• Alleles can be different – heterozygous• If only one allele is present – hemizygous

– Case in males for genes on X and Y chromosomes

Genetic Concepts

Allele – G vs g; W vs w

At the G locus either the G or g allele may be present on a given homologue of a homologous pair of chromosomes

Genetic Concepts• Genome– Collection of all genetic material of organism

• Genotype– Set of alleles present in the genome of an organism

• Phenotype– Result of Gene Expression– Genes (DNA) are transcribed into RNA– mRNA is translated into protein, tRNA & rRNA work in

translation process– Biochemical properties of proteins, tRNAs & rRNAs

determine physical characteristics of organism

DNA

Gene

Transcription

Translation

RNA (messenger RNA)

Protein(sequence ofamino acids)

Functioning of proteins within livingcells influences an organism’s traits.

Gene Expression

Wing cells

Lots of pigment made Little pigment made

Pigmentmolecule

(b) Cellular level

Pigmentation gene,dark allele

Pigmentation gene,light allele

Transcriptionand translation

Highly functionalpigmentation enzyme

Poorly functionalpigmentation enzyme

(a) Molecular level

Mutation & Phenotypic Variation

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Medical GeneticsWhen studying rare disorders, 6 general

patterns of inheritance are observed:

• Autosomal recessive• Autosomal dominant• X-linked recessive• X-linked dominant• Codominant • Mitochondrial

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Medical Genetics (cont.)

Autosomal recessive

• The disease appears in male and female children of unaffected parents.

• e.g., cystic fibrosis

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Medical Genetics (cont.)

Autosomal dominant• Affected males and

females appear in each generation of the pedigree.

• Affected mothers and fathers transmit the phenotype to both sons and daughters.

• e.g., Huntington disease.

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Medical Genetics (cont.)

X-linked recessive• Many more males than

females show the disorder.

• All the daughters of an affected male are “carriers”.

• None of the sons of an affected male show the disorder or are carriers.

• e.g., hemophilia

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Medical Genetics (cont.)

X-linked dominant • Affected males pass the

disorder to all daughters but to none of their sons.

• Affected heterozygous females married to unaffected males pass the condition to half their sons and daughters

• e.g. fragile X syndrome

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Medical Genetics (cont.)

Codominant inheritance

• Two different versions (alleles) of a gene can be expressed, and each version makes a slightly different protein

• Both alleles influence the genetic trait or determine the characteristics of the genetic condition.

• E.g. ABO locus

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Medical Genetics (cont.)

Mitochondrial inheritance

• This type of inheritance applies to genes in mitochondrial DNA

• Mitochondrial disorders can appear in every generation of a family and can affect both males and females, but fathers do not pass mitochondrial traits to their children.

• E.g. Leber's hereditary optic neuropathy (LHON)