12. genetic pedigree one

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Pedigree AnalysisONE

SDK

December 8, 2014


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Learning Objectives

Pattern of Inheritance

Define common terms used in genetic pedigree

What are the goals of pedigree analysis

What a genetic pedigree is

How to draw a human genetic pedigree

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Pattern of inheritance

Pattern of inheritance is broken in to two major parts.Classical mendelian

AutosomalDominant

Recessive

Sex(X)LinkedDominant

Recessive

Non classical----------Mitochondrail

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Terms

Traitcharacteristic of an organism

Genea heredity unit that codes for a trait.

Alleledifferent gene forms(Alternative forms of genes)Allelic genes do not necessarily carry the same information.

For example; gene of black and gene of brown color are allelic

genes, because they control one trait (ani mals color).

Nonallelic genes: Genes that control different traits such as genes thatcauses hemophilia and color Blindness are X-chromosome linked genes,they are nonallelic genes.

Homozygous: If alleles on homologous chromosomes are

similar for a single locus (BB or bb), the individual Genotype iscalled homozygous

Heterozygous: If the alleles are different for a locus (Bb; one isdominant & the other is recessive), the individual genotype iscalled heterozygous

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Terms

Dominantthe gene that is expressed (shown) whenever it ispresent.

In this case one of the gene at one loci is defective and this willdisturb(decrease) the action of the other normal gene of the otherchromosome and brought upon abnormal phenotype.

Recessivethe gene that is hidden. It is not expressed unlessa homoz ous condition exists for the ene.

In this case also one of the gene at one loci is defective butthis will not disturb(decrease) the action of the othernormal gene of the other chromosome rather other genewill function normally and give a normal phenotype

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Terms

In general the

Dominant Gene : Code for Structural protein

such as receptors, defect in one allele is enough

to produce diseaseRecessive Gene: Code for Functional proteins

such as Enzymes .defect in one allele is do not

produce disease

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Dominance is not always complete

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Incomplete dominance

If the offspring express a mixture of the traits of parents, the genes that control these traits are

incomplete dominant alleles.

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Codominance

When two all aellels for single locus are

expressed in hybrid; heterozygous individuals,

they are called co-dominant alleles.

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Linked & Non linked Genes

Linked genes: When two genes are close together on the

same chromosome, they do not assort independently

and are said to be linked. Linked genes have a

recombination frequency that is less than 50%.

Non Linked genes: When two genes located on

different chromosomes assort independently and have a

recombination frequency of 50%.

The closer together two genes are, the more likely they will be inherited

together.

Cross-over frequencies are related to distances between genes.

The higher the frequency, the further the genes are apart

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Cross-over frequencies can be converted into map units.

Ex: A 5% cross-over frequency equals 5 map units.

gene A and gene B cross over 6.0 percent of

the time

gene B and gene C cross over

12.5 percent of the time

Gene linkage

gene A and gene C cross over 18.5 percent of the time


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Draw a linkage map based on the

following cross over percentages:

AB = 8%

BC = 10%

AC = 2%

8.0 2.0

B A C

8.0 + 2.0 = 10.0


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Terms

Homozygoustwo identical (same) alleles for agiven trait (TT) also called purebred.

Heterozygoustwo different (opposite) allelesfor a given trait (Tt), also called hybrid.

Gametesexual reproductive cell (sperm &

egg .

Fertilizationthe fusion of two gametes.

Phenotypephysical trait of an organism.

Genotypethe genes present in the cell.

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Remember

Homozygous = AA or aa = purebred

Heterozygous = Aa = hybrid

Dominant = capital letter (A)

Recessive = lower case letter (a)

Genotype = alleles involved (AA, aa, or Aa)

Phenotype = trait expressed (blue or green)

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Goals of Pedigree Analysis

1. Determine the mode of inheritance:1. Dominant

2. Recessive

3. Sex-linked4. Autosomal

5. mitochondrial, maternal effect.

2. Determine the probability of an affected

offspring for a given cross.

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Basic Symbols

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More Symbols

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What is a Genetic Pedigree?

Pedigree is a diagram of family relationships that uses symbols to

represent people and lines to represent genetic relationships

A genetic pedigree is an easy way to track your family traits.

It looks like a family tree, but also contains information about the

A doctor or geneticist might draw a family pedigree if some one

had a family history of a particular disease.

With this information they could see how the disease is inherited

and calculate the probability of passing on the disease to future

mode of inheritance (dominant, recessive, etc.) of genetic

diseases.

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children.


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Generations

I

II

1 2

This is an example of a family tree showing 3 generations of family

members.

The roman numerals (in red) on the left indicate the generation each person

belongs to.

III

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1

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.

Notice it restarts at 1 every new generation.

Older siblings are on the left and younger siblings are on the right in

descending order.

Using this system, the individual at the bottom of this pedigree is III:1.


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Symbols

Each of the individuals indicated by a circle is a woman and

each of the squares represents a male family member.

Individual III:1 is a male.

Common reasons for this would be, miscarriages or early death,

babies given up for adoption, a child that has not been born yet.

These individuals can be noted by using a diamond symbol ( )

instead of a square or circle.

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Marriage Lines

The lines highlighted in redindicate individuals that have hadchildren together. Even thoughwe call them marriage lines itdoes not matter if they aremarried, were married, or were

I

II

1 2

never married.

It is important to realize that timehas no meaning on a geneticpedigree, therefore we do not

usually indicate if someone hasdied or been divorced.

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III

2 31

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Children LinesThe lines highlighted in red are

children lines

The marriage line that they areconnected to from above indicateswho gave them their genetic traitsrather than who raised them.

If a couple has more than onechild together then we split the

child line as the green highlighted

1 2

I

.simply require a longer line withmore lines coming down from it.Thus II:2 and II:3 are children of I:1

and I:2, but II:1 married into the

family and has different parents. Wealso know that II:2 is older than hissister (read left to right). However,we dont know anything about therelative age of II:1 even though sheis on the left since she married intothe family.

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2 31

1

II

III


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Adoptions

I

1 2

The red line (dashed) children lines to denote achild that is not related biologically (adopted).

In this example, the couple adopted a son.

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II

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Twins Twins are another fairlycommon occurrence. However,there are two kinds and from a

genetic standpoint it is veryimportant to know thedifference.

In the case of identical twins, thetwo siblings have the same DNA.

To show this we split the siblingline at an an le. The red

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1 2

highlighted line is an example ofthis.

In the case of fraternal twins,although born at the same time, the

siblings are no more related thanany other siblings. Thus, they aredrawn the same as any siblings.The green highlighted lines showthis.

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II

1 2

3 4


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Penetrance

Penetrance - the frequency of expression of an

allele when it is present in the genotype of the

organism.

the trait, the trait is said to be 90% penetrant.

Or 10% reduce penetrance.

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Variable Expressivity

Expressivity is the variation in allelic expression

when the allele is penetrant.

Not all phenotypes that are expressed are manifested

to the same degree.

For polydactyly, an extra digit may occur on one or

more appendages, and the digit can be full size or just

a stub.

Therefore, when the P allele is present it expresses

variable expressivity.

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Pleomorphisim

Gnees acuses disese in more than one sysytem.

Such as Marfan Syndrome It involve

Occular abnormality

V pro ems an

Skeletal abnormalities.

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INCOMPLETE PENETRANCE

Incomplete penetrance should never be confused with variable expressivity.In diseases with variable expressivity the patient always expresses some of

the symptoms of the disease and varies from very mildly affected to very

severely affected.

In autosomal dominant diseases with incomplete penetrance, the person

either expresses the disease phenotype or he/she doesn't.

Incom lete enetrance and variable ex ressivit are henomena associated

only with dominant inheritance, never with recessive inheritance.

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The pedigree illustrates incomplete penetrance in a

known autosomal dominant disease.

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Evidence For Autosomal Dominant Inheritance:

The disease is passed from the father (II-3) to the son (III-5), this never

happens with X-linked traits.

The disease occurs in three consecutive generations, this never happens

with recessive traits.

Males and females are affected, with roughly the same probability.

However, II-1 does not express the disease.

He must have inherited the mutant allele because he passed it on to two

children, III-1 and III-3.

II-1 is a classical example of incomplete penetrance, he has the allele for

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1. The Punnet Square

In Ahmad family Disease(A) is inherited as aautosomal dominant disease.

In this family, a heterozygous male marries a

homozygous recessive female.

1. This disease is inherited as a autosomal dominant disease

1. Autosomal dominant means that any person with a dominant

allele will be affected.

2. A heterozygous male marries a homozygous recessive female.

1. Heterozygous male Aa (heterozygous means one of each

allele)

offspring.

What is the chance they will have an

unaffected child?

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2. Homozygous recessive female aa (homozygous means two of

the same allele, here two of recessive alleles)

3. Draw a Punnett square of the possible offspring

1. Set up the Punnett square with the genotypes of the above two parents.2. What is the chance they will have an unaffected child?


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Father A a

Mother

a Aa aa

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a a aa

Aa are affected because they have a dominant gene

So 2 of 4 (2/4 = ), there is a 50% chance that anychild would have the disease and 50% will be normal.


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2. The Punnet Square

This disease is inherited as a autosomalrecessive disease.

A heterozygous male marries a heterozygous

female.

Explanation

This disease is inherited as a autosomal recessive disease

Autosomal recessive means that any person with a two

recessive allele will be affected.

A heterozygous male marries a heterozygous recessive

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offspring. What is the chance they will have

an unaffected child?

.

Heterozygous male Aa(heterozygous means one of each allele)

Heterozygous recessive female AaDraw a Punnett square of the possible offspring

What is the chance they will have an unaffected child?


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Father A a

Mother

A AA Aa

a Aa aa

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What is the chance they will have an unaffected child?

aa are affected because they have two recessive gene

So 1 of 4 (1/4) AA Completely normal

So 1 of 4 (1/4) aa homozygous Completely abnormal

So 2 of 4 (1/4) Aa heterozygous carrier

There is a 25% chance that any child would have the disease.


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Steps in Pedigree Analysis

1. Analyze whether the pedigree belongs to a

dominant or recessive group.

1. Dominant

a) Affected person must have affected parentsvery generat on w e a ecte

2. Recessive

a) Parents will be not affected

b) There will be skip generations

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Steps in Pedigree Analysis

1. Autosomal . Both boys and girls will be involved. Dominant

Disease must be in multiple generation.

Disease person must have an affected parents.

Male & female are equally affected

Recessive Disease have skip generation.

Disease person must not have an affected parents.

Because autosomes are involved , Male & female are equally affected

2. X-linked

Dominant Affected male will transmit the character to all daughters but not to sons

Affected female will transmit the character to Half sons and Half daughters.

Recessive

No male to male transfer

Affected male will be more than female

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1. Autosomal Dominant Inheritance

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Autosomal Dominant

Appears in both sexes with equal frequency

Both sexes transmit the trait to their offspring

Does not skip generations

unless they posses a new mutation

When one parent is affected (het.) and the other

parent is unaffected, approx. 1/2 of the offspring willbe affected

Unaffected parents do not transmit the trait

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Autosomal Dominant Traits

A dominant condition is

transmitted in unbroken descent

from each generation to the next. A typical pedigree might look like

this:

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Autosomal Dominant Traits

Huntington disease is a progressive nerve degeneration, usually beginning aboutmiddle age, that results in severe physical and mental disability and ultimately in

death

Every affected person has an affected parent

~1/2 the offspring of an affected individual are affected

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2. Autosomal Recessive Traits

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Autosomal Recessive

Appears in both sexes with equal frequency

Trait tend to skip generations

Affected offspring are usually born to unaffected

arents

When both parents are hetrozygout, approx. 1/4 of the

progeny will be affected

Appears more frequently among the children ofconsanguine marriages.

The punnet square will be like this

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Autosomal Recessive

A recessive trait will only show

up when homozygous.

Most eo le are heteroz ouscarriers

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Autosomal Recessive Traits

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Abetalipoproteinemia.

Acute fatty liver of pregnancy

Alkaptonuria.

Congenital hepatic fibrosis.

C stic Fibrosis.

Leukocyte Adhesion Defect.

Nieman Pick Disease.

Rotor syndrome.

Situs Inversus.

Sickle cell Disease and

Cystinosis, Cystinuria.

Dubin-Johnson syndrome.

Fanconi Anemia.

Trait.

Thalasemia.

Wilson's Disease.

Xeroderma pigmentosa

Friedrech's Ataxia.

Glycogen storage diseases.

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Albinism = absence of pigment in the skin, hair, and iris of the eyes

Most affected persons have parents who are not themselves affected; theparents are heterozygous for the recessive allele and are called carriers

Approximately 1/4 of the children of carriers are affected

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CYSTIC FIBROSIS

Cystic fibrosis (CF) is a genetic condition that affects many organs in thebody: especially the lungs, pancreas and sweat glands.

A build-up of thick, sticky mucus in these organs leads to respiratory

problems, incomplete digestion and increased salt loss from the sweat

glands.

CF most commonly affects people who are of Northern European or UK

descent, is also fairly frequent in people whose ancestry is Southern

European and Middle Eastern.

In CF the CFTR gene(salt-transport gene) that contains the information for

the production of the protein that transports salt in and out of the cells is

absent that result in thick secretions loaded with salt.

The CFTR gene is located on chromosome 7, an autosome This thick secretions block air passages, pancreatic and intestinal ducts will

impair the function of these organs, Indigestion wt loss and increased loss of

Salts.

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Presentation of Disease

Mucous in the airways cannot be easily cleared from the lungs.

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Tay-Sachs

Tay-Sachs is a recessive lethal disease in whichthere is neurological deterioration early in life.

This disease is rare in the population overall but

is found at relatively high frequency in.

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An apparently normal woman whose maternal uncle hadthe disease is trying to determine the probability that she

and her husband(who is also normal) could have an

affected child.

Her father does not come from a high-risk population.

Tay-Sachs

Her husbands sister died of the disease at an early age.

Draw the pedigree of the individuals described. Include

the genotypes where possible.

T = normal allele;

t = Tay-Sachs allele

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Tay-Sachs

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Thank You

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12. genetic pedigree one

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