1 inheritance (i)

8/3/2019 1 Inheritance (I)

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Inheritance

Dr. Zeyad Akawi Jreisat, M.D., M.A., Ph.D.


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AUG TAAIntro

n

Exon

mRNA

Protein

Transcription

Translation


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Chromosomal Theory of Inheritance

Chromosomes contain the genetic material that istransmitted from cell to cell and from parent tooffspring

Chromosomes are replicated and passed along

generation after generation from parent to offspring. The nuclei of most eukaryotic cells contain

chromosomes that are found in homologous pairs.

During gamete formation, different types of

chromosomes segregate independently of eachother.

Each parent contributes one set of chromosomes toits offspring.


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- Mendelian

- Autosomal dominant

- Autosomal recessive

- X-linked recessive

- X-linked dominant

- Nontraditional

- Mitochondrial

- Imprinting

- Uniparental disomy

- Mosaicism

- Multi-factorial

Types of Inheritance


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Symbols for Pedigrees


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Symbols for Pedigrees


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Pedigree: Expression of segregation or transmission oftraits within families.

Proband or index case: 1st family member seekingmedical attention (P).

Generation: Roman numbers (I, II, etc.).

Individuals: Arabic numbers (1,2, etc.).

Age: Next or below the symbol.


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In order to understand Mendalian inheritance,several essential terms must first be defined


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Locus: A specific position on a chromosome.

Alleles: alternative forms of a gene, or of a DNA

sequence, at a given locus.

Homozygous: both alleles at a locus are identical.

Heterozygous: both alleles at a locus are different.

A compound heterozygote: two different mutant

alleles at a given locus.

Double heterozygote: One mutant allele at each of twodifferent loci.


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Genotype: the genetic constitution or composition of anindividual.

Phenotype: the observed results of the interaction of the

genotype with environmental factors.

Genotype & Phenotype: are a musical analogy.

Mendelian diseases: the result of a single mutant genethat has a large effect on phenotype, inherited in a simplepatterns.

Autosomal diseases: Encoded by genes on one of the22 pairs of autosomes (non-sex chromosomes).

X-linked: encoded by a mutant gene on the Xchromosome.


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A Comparison of Homologous Chromosomes


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Homozygous:

Both alleles at a

locus are thesame.

Heterozygous:

At the locus one

gene is the wildtype and the other

mutant.

Compound

heterozygote:

Both allele areabnormal but

different

variations.

or

N N Ab Ab N Ab Ab1 Ab2


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Mendelian genetics

Principle of segregation: Sexually reproducingorganisms possess genes that occur in pairs andthat only one member of this pair is transmitted tothe offspring

Principle of independent assortment: genes atdifferent loci are transmitted independently. In areproductive event, a parent transmits one allelefrom each locus to its offspring and the allele

transmitted at one locus has no effect on whichallele is transmitted at the other locus


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What is a trait?

WWor

Wwww

Widows peak


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How do we inherit a single trait?

We have to know the mode of inheritance

Dominant allele It is expressed when present

It is designated with a capital (uppercase) letter

An example is W for widows peak.

Recessive allele

It is only expressed in the absence of a dominantallele.

It is designated with a lowercase letter indicates

An example is w for continuous hairline.


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Proper use of the Punnett Square

A Punnett square can thenbe used to determine thephenotypic ratio among theoffspring

The punnett square can be

used when it is hard toimagine the phenotypicratio from any cross (i.e. YyX Yy).

Single gene: Yy X Yy = 3:1

Two genes: YyZz X YyZz =9:3:3:1


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Basic concepts of Probability

Laws of probability alone can be used to determineresults of a cross.

The laws are:

Multiplication rule: the probability that two ormore independent events will occur together isthe product of their chances occurring separately.

Addition rule: the chance that an event that canoccur in two or more independent ways is thesum of the individual chances.


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In the cross of Ww x Ww, what is the chance ofobtaining either a W or a w from a parent?

Chance of W = , or chance of w =

The probability of these genotypes is:

The chance of WW = x =

The chance of Ww = x =

The chance of wW = x =

The chance of ww = x =

The chance of widows peak (WW, Ww, wW) is + + = or 75%.


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Genotype versus Phenotype

Genotype refers to the genes of an individualwhich can be represented by two letters.

Homozygous means that both alleles are the

same; for example, WW stands for homozygous dominant

ww stands for homozygous recessive.

Heterozygous means that the members ofthe allelic pair are different for example,

Ww, a heterozygote


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Genotype versus Phenotype

Phenotype refers to the physical or observablecharacteristics of the individual.

Both WW and Ww result in widows peak,

the phenotype is a widow's peak

however, we have two genotypes resulting in thesame phenotype.

ww results in a straight hairline in this case, the phenotype can only result from

one genotype


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Genotype and gene frequency

The prevalence of many genetic diseases variesconsiderably from one population to another.

The variation is due to the difference in proportiongenotypes and alleles in a population.

Under simple conditions these frequencies can beestimated by direct counting.

(MM: 64, MN: 120 and NN: 16) Total 200 subjects

Genotype frequency = Genotype count/Total MM = 0.32; MN = 0.60; NN = 0.08 and the sum

equal 1.

G (All l ) f i il


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Gene (Allele) frequencies are easilyestimated from genotype frequencies

How were allele frequencies estimated ?

For Eskimo - Freq .of M = (0.835 + (0.5 x 0.156 )) = .913

Freq. of N = (0.009 + .(0.5 x 0.156 )) = .087


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Example

Imagine that we have typed 200 individuals in a population forMN blood group, of these we have 64 with MM genotype, 120with MN genotype and 16 with NN genotype.

What is the genotype frequency?It is obtained simply by dividing each genotype count by thetotal number of subjects, for MM genotype it is 64/200 = 0.32for MN genotype is 120/200 = 0.6 and for NN genotype is16/200 = 0.08 the sum of these frequencies must equal 1


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What is the gene frequency?

The gene frequency for each allele, M and N can be obtainedby the process of gene counting.

For M, each MM homozygous has two M alleles while eachMN heterozygous has one allele therefore, the number ofgenes is

(64 X 2) + 120 = 284 genes

For N, each NN homozygous has two N alleles while eachMN heterozygous has one allele therefore, the number ofgenes is

(16 X 2) + 120 = 152 genes

in total there are 400 genes at the MN locus

To obtained the frequency of M, we divide the number of M

allele by the total number of alleles at that locus248/400 = 0.62

The same for the N allele, 152/400 = 0.38

The sum of the two frequencies must equal 1


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Classification of genetic disorders

Single-gene disorders

Chromosome disorders

Multifactorial disorders


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Single-gene disorders

Caused by mutations in individual genes.

Mutations may be present in only one or both copiesof a gene.

Usually exhibit obvious and characteristic pedigreepatterns.

Affect 2% of population sometime over an entire lifespan.


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Many important and well-understood genetic diseases are theresult of a mutation in a single gene.

Single-gene or monogenic traits are also known as Mendeliantraits.

The variation in traits is caused by the presence of differentalleles at individual loci

Mendels key contributions to genetics were The principles of segregation

Independent assortment

The effects of one allele may mask those of another(dominance and recessiveness)

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