pedigree drawing 2014

DR Jai Prakash soni Curriculum Vitae

professor

Head unit IV

Dep Pediatrics Dr S N Medical , Jodhpur

Contact: +91-9828034098

E-mail: [email protected]

Education

• M.B.B.S in 1983 Dr S.N. Medical college, Jodhpur

• M.D. Pediatric 1987, Dr S. N. Medical college, Jodhpur

Major posts/responsibilities:

• Organizing secretary of Live Workshop on Fetal medicine and

interventional sonography in 2009 and 2010 at Jodhpur.

Thalassa – Gen 2012 at Jodhpur

Special training:

• Specialized training Pediatric cardiology

at AIIMS, Delhi

Twinty four publications in national journals

Pediatric cranial Sonography and fetal echocardiography – field of

special interest.

Speaker : First international congress on fetal medicine, New Dehli

Dr. Jai Prakash Soniprofessor

Unit head IV

Dr S N Medical collegejodhpur

Pedigree

Pedigree - “ pie de grue ” (Fr. crane’s foot)

It is a graphic depiction of relation

between family

members, that is

How they are

biologically/legally

related to

each other through generations.

Pedigree

chart

Serve as a

reference

of

social and

biological

relationships.

Pedigree is thesymbolic language

used for clinical genetic services

and

human genetic research.

To determine the

mode of

inheritance:

Autosomal Dominant

Autosomal Recessive

Partial dominance

Sex-linked

Mitochondrial

Help to

determine

the risk or

probability

of an

affected

offspring

for a given

cross. Determining genotypes for various

individuals

How different symbols are used

while drawing

Pedigree Chart ?

Pedigree Standardization Task Force

Organized by the National Society of Genetic Counselors

Recommendations for universal standards in human pedigree nomenclature

Had provided Guide lines

For drawing pedigree.

While drawing “Pedigree chart”

One should follow rule of thumb

Symbols used for drawing Pedigree chart are

Male family member is

represented by a square .

•American Journal of Human Genetics 56:745-752, 1995

Female family member is

represented by a Circle .

Gender not Specified

Other Symbols used in a Pedigree Chart are

X-linked – Carrier are depicted Central dot in a circle.

Autosomal carrier Represented by central vertical line.

Deceased/Death sib is represented with slash

Shaded circles or squares represents affected individuals.


Affected fetus

Representation of 2 or more conditions

Normal relation between couple is

demonstrated by straight line

Consanguineous mating is

demonstrated by two Parallel lines

Broken Relationship between couple

is demonstrated by broken line

Relationship Between Couple is

Depicted by connecting lines

Marriage line

Divorce

consanguineous

Relationships between

parent & offspring is depicted as

The pedigree of Biological parents

with one sib will be

Age Personally examined

Descent line

Family tree

•American Journal of Human Genetics 56:745-752, 1995

Relation ship between parent’s and sib is

demonstrated by Connecting line.

o Vertical line drawn

represents a child.

Horizontal line across sib will represent

total number of children in family(siblings).

Relationships between

parent & offspring is depicted as

The pedigree of Biological parents

with one sib will be

When child is Adopted From family Member

Pedigree will like as shown below

?If Biological parents not known the pedigree

Will be depicted as

When couple do not have children

Pedigree will be depicted as

[ ]

When child is Adopted out of the family Members

Pedigree will be depicted as

Symbols for Twin sib

Twins

Monozygotic

Dizygotic

Unknown

zygocity

?

D

P

P

P

D

Donor sperm

Donor ovum

S

P

Surrogate only

D

D

P

P

Surrogate ovum donor

Surrogate ovum donor

P

P

Planned adoption

D D

[ ]

Donor sperm and ovum

Rule of thumb while drawing a pedigree chart.

Tips for drawing

Male partner is drawn to the left of female.

Family member of each generation should be on the same plane

Tips for drawing

Siblings are drawn in birth order.

Each generation is identified by Roman numerals

I

II

III

IV

by Arabic numerals

I

II

III

IV

1 2 3 4 5

Individuals in each generation are

Numbered from the left

Pedigree chart

The affected individuals are denoted first by Generation then by their Arabic numbers

II3

IV2 and IV4

I

II

III

IV

1 2 3 4 5

Usually three generations pedigree is drawn for fruitful

conclusion.

Generations are extend back as far as possible if a significant health problem is identified.

How to draw a pedigree ? “Example”

Anita have two brothers and two sisters.

She married to Deepak.who is her maternal aunt’s son

(first cousins).How this pedigree will be drawn ?

Anita Sunil Meeta Anil SunitaDeepak

Reeta

Anita have two brothers and two sisters. She married to Deepak.who is her maternal aunt’s son

(first cousins)

Anita and Deepak are expecting their second child.

Their first child, Rahul has cystic fibrosis.

How Pedigree will be look like ?

P

Anita

Rahul

Deepak

cystic fibrosis second pregnancy

Anita has two brothers, Anil, Sunil and a sister Sunita.


Anita has two brothers, Anil, Sunil and a sister Sunita.

P

Anita

Rahul

Deepak

P

Anitha Sunil Meeta Anil Sunitha

PinkyRahul

Deepak

Reeta

PP

Anitha Sunil Meeta Anil Sunitha

PinkyRahul

Deepak

Reeta

Sunita

Anil and Sunita are unmarried.

Sunil is married to an unrelated woman Meeta and has a two year old

daughter Pinky.


P

Anita Sunil Meeta Anil Sunita

PinkyRahul

Deepak

Reeta

Anil and Sunita are unmarried. Sunil is married to an unrelated woman Meeta

and has a two year old daughter Pinky.

“Drawing A complete pedigree is often a work of great labour, and in its finished

form is frequently a work of art.”

Karl Pearson (1912)

Mother’s genes Father’s genes

Child’s genes

Under what circumstances interpretation of a pedigree

Is required ?

Interpretation of pedigree is required

for Various MENDELIAN inheritance

patterns ------ Autosomal dominant

e.g., Huntington’s Disease

Autosomal recessive

e.g., PKU, Tay-Sachs, albinism

X-linked recessive

e.g., color-blindness, hemophilia

X-linked dominant

e.g., hypophosphatemia

Y-linked -LERI WEIL DYSCHONDROSIS

Organelle - Mitochondrial disorders

HOW TO READ THESE VARIOUS MENDELIAN INHERITANCE

PATTERNS ON A PEDIGREE CHART ?

It is not magic to understand pedigree, But one require little practice to understand how to read pedigree ,

What type of inheritance is This ?

AUTOSOMAL DOMINANT PEDIGREE

1) Both sexes are involved

2) Generation not skipped

3) "Vertical" transmission

4)Spontaneous mutation

5)50% risk for affected child, if parent affected

Counseling The risk of passing an Autosomal disorder to

next generation from an affected Person is 50%,

but manifestation of disease is influenced by

1.Disease penetratnce – all & non phenomenon

2.Variable expression

3.Anticipation

4.pleiotropy – different mutation in same gene

cause different manifestation-

LMNA gene ( encode lamin A/C) & X filamin A

gene

Emery –dreifuss muscular dystrophy, limb girdle

muscular dystrophy, dilated cardiomyopathy,

Hutchinson Gilford progeria.

WHAT IS DOMINANCE?

Dominance & recessiveness are relative term and are used

Only when one allelle is compared with the other

On chromosome at each locus there can be many genes,

Which are known as “ALLELES”

Person with Genotype AA, Aa (Heterozygote) “ALLELES”

Phenotype will be similar, as A dominant over

Normal “a” ( wild type) allele.

Such manifestation of gene in heterozygote state are

known as “Dominant” gene.

Person with Genotype aa (Homozygote) “ALLELES”

Phenotype will be of Normal

Dominant

If both partners are affected & have an unaffectedchild, it must be a heterozygous dominant pedigree:

“A” is the dominant mutant allele and

“a” is the recessive wild type allele.

It means both parents are “Aa” and the normal childis “aa”.

If every child is affected than bot parents should behomozygous and will have “AA” dominantgenotype.

Manifestation of Dominant gene depends on –

Penetrance : though person carry mutant gene but either gene donot manifest or

disease manifetst at late age – Huntington chorea,

Myotoinic dystrophy

Spinocerebellar ataxia

Thus risk of having clinically affect offspring is < 50%.

Variable expressivity: The severity of diseases may very in affected person of a

family. One can have all features while other may have only

one feature – Neurofibromatosis.

This is because of interaction between causative “Gene” and modifier “Gene” and

environment. It means single gene disorder are not truly govern by

one gene but real senesce they are oligogenic.

Manifestation of Dominant gene depends on –

Anticipation : If the severity of disease increases as it is passed

down the generation.

Myotonic dystrophy –

Grand parents at old age – cataract and muscular weakness

Mother - mild muscle weakness

Offspring - severe hypotonia during neonatal period.

AUTOSOMAL DOMINANT diseases• HUNTINGTON DISEASE

• NEUROFIBROMATOSIS

• MYOTONIC DYSTROPHY

• TUBEROUS SCLEROSIS

• POLYCYSTIC KIDNEY

• HEREDITARY SPHEROCYTOSIS

• VON WILLEBRAND DISEASE

• MARFAN SYNDROME

• EHLERS-DANLOS SYNDROMES(some)

• OSTEOGENESIS IMPERFECTA

• ACHONDROPLASIA

• FAMILIAL HYPERCHOLESTEROLEMIA

• ACUTE INTERMITTENT PORPHYRIA

Pseudo dominance

AUTOSOMAL RECESSIVE PEDIGREE

1) Both sexes are involved

2) "Horizontal" transmission

3) Parents are heterozygous for trait

4) For affected child risk is 25% risk

with each pregnancy.

WHAT IS RECESSIVENESS?

Dominance & recessiveness are relative term and are used

Only when one allelle is compared with the other.

On chromosome at each locus there can be many genes,

Which are known as “ALLELES”

Person with Genotype Aa (Heterozygote) “ALLELES”

Phenotype will not have manifestation of


Only when Person’s Genotype is “aa” (Homozygote)

“ALLELES” or compound Hetreozygocity.

Phenotype will have manifestation of


aa

aa

Aa

Aa

Aa

Only a recessive trait can skip a generation

If neither of these events occurs in

a pedigree then trait could be dominant.

AUTOSOMAL RECESSIVE

CF PKU GALACTOSEMIA HOMOCYSTINURIA LYSOSOMAL STORAGE Α-1 ANTITRYPSIN WILSON DISEASE HEMOCHROMATOSIS GLYCOGEN STORAGE

DISEASES

Hgb STHALASSAEMIASCONG. ADRENAL HYPERPLASIAEHLERS-DANLOS (some)ALKAPTONURIANEUROGENIC MUSC. ATROPHIESFRIEDREICH ATAXIASPINAL MUSCULAR ATROPHY

Recessive

If two unaffected people have an affectedchild, it is a recessive pedigree:

“R” is the dominant wild type allele and

“ r” is the recessive mutant allele.

Both parents are Rr and the affected child is rr.

SEX LINKED PEDIGREE

1) Only Males are affected

2) Generation skipping does not matter.

SEX (“X”) LINKED

If only male partner is affected then all his sons will be normal and daughters will be carrier.

The “Y” chromosome is not homologous to the “X” that’s why the concept of

dominant / recessive has no meaning here.

Heterozygous females have no phenotypic expression (carriers)….usually, this means autosomal “recessive”, right ?

Pedigree of an X-linked recessive disorder

Son not

affected

Daugther

carrier

1/2

grandsons

affected

Father affected

SEX (“X”) LINKED

DUCHENNE MUSCULAR DYSTROPHY

HEMOPHILIA , A and B

G6PD DEFICIENCY

AGAMMAGLOBULINEMIA

WISKOTT-ALDRICH SYNDROME

DIABETES INSIPIDUS

LESCH-NYHAN SYNDROME

FRAGILE-X SYNDROME

are characterized by the following pedigree

pattern:

(1) Affected males transmit the disease to all

their daughters but none of their sons.

unlike dominant autosomal disorders where

daughters and sons have an equal probability

to inherit the disease.

X-linked dominant disorders

(2) Affected females are mostly heterozygous.

When married to unaffected males, they transmit

the disease to 50%(1/2 )of their sons and (1/2) of

their daughters (same pattern as for autosomal

dominant disorder).

X-linked dominant disorders

Note: X-linked dominant disorder are rare

traits in human . Ex: Hypophosphatemia:

low levels of inorganic phosphate in the

blood.)

Diagnosis is complicated by the process of

X inactivation in females.

Y-Linked Inheritance

Traits on the Y chromosome are only found in males, never

in females.

The father’s traits are passed to all sons.

Dominance is irrelevant: there is

only 1 copy of each Y-linked gene .

LERI WEIL DYSCHONDROSIS

Mitochondrial Genes

Mitochondria are only inherited from the mother.

If a female has a mitochondrial trait, all of her (male and females ) offspring inherit it.

If a male has a mitochondrial trait, none of his offspring inherit it ; as sperm Head do not have mitochondria. .

Note that only one allele is present in each individual,

so dominance is not an issue.

MULTIFACTORIAL INHERITANCE

Multi-”FACTORIAL”, not just multi-GENIC

“SOIL” theory

Common phenotypic expressions governed by “multifactorial” inheritance

Hair color

Eye color

Skin color

Height

Intelligence

Diabetes, type II

Features of Multifactorial inheritance

Expression determined by NUMBER of genes

Overall chance of transmission is 5% if 1st degreerelatives is affected.

This risk of transmission will increased (>5%) ifmore than one child is affected.

“MULTIFACTORIAL” DISORDERS

Cleft lip, palate

Congenital heart disease

Coronary heart disease

Hypertension

Gout

Diabetes

Pyloric stenosis

MANY, MANY, MANY, MANY MORE

The Punnett square

The Punnett square is a tabular summary of every

possible combination of one maternal allele with one

paternal allele for each gene being studied.

It is named after Reginald C. Punnett, who devised the

approach.

It is used by biologists to determine the probability of an

offspring's having a particular genotype.

http://en.wikipedia.org/wiki/Allele

http://en.wikipedia.org/wiki/Reginald_Punnett

http://en.wikipedia.org/wiki/Biology

http://en.wikipedia.org/wiki/Probability

http://en.wikipedia.org/wiki/Genotype

The Punnett square

It is used to simulate segregation of alleles into

gametes by meiosis and recombination of new

genotypes fertilization.

It predicts the genotypes and phenotypes of the

offspring of any two parents (when all possible

sperm are given an equal chance to fertilize all

possible eggs).

Summary

Pedigrees are family trees that explain your genetic history.

Pedigrees are used to find out the probability of a child having a disorder in a particular family.

To interpret a pedigree, it is essential to determine - the disease condition is

autosomal or X-linked

And

dominant or recessive.

pedigree drawing 2014

Health & Medicine