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GENETICS

&
MOLECULAR BIOLOGY
PART II
AGENDA

Pedigree analysis

Inheritance of Human traits – Brown Eyes,


Polydactyly, Diabetes insipidus, Phenylketonuria,
Sickle cell Anemia,

Eugenics and Genetic Counselling.

Summary

References
Pedigree analysis….
What is Pedigree?

To determine the mode of inheritance of phenotypes in humans,


where designed crosses are not possible and where relatively few
offspring are available for study. The way out for such inheritance
study is to construct a family tree, indicating the presence or absence
of the trait in question for each member of each generation. Such a
family tree is called a pedigree.

Pedigree is symbolic representations of family relationships and


inheritance of a trait

Pedigree analysis

Analysis of family tree to predict how the trait under study is inherited.

Analysis of pedigrees using knowledge of Mendelian principles allows


us to;
–Determine whether the trait has a dominant or recessive pattern of
inheritance
–Determine whether the gene in question is located on an X or Y
chromosome or on an autosome.

This kind of information can be used to predict risk


Pedigree analysis….
Inheritance of Human traits –

Mendelian traits, or single gene disorders, fall into 5 categories or modes of inheritance
based on:

• where the gene for the trait is located and


• how many copies of the mutant allele are required to express the phenotype:

1. Autosomal recessive inheritance (the locus is on an autosomal chromosome and


both alleles must be mutant alleles to express the phenotype)

2. Autosomal dominant inheritance (the locus is on an autosomal chromosome and


only one mutant allele is required for expression of the phenotype)

3. X-linked recessive inheritance (the locus is on the X chromosome and both alleles
must be mutant alleles to express the phenotype in females)

4. X-linked dominant inheritance (the locus is on the X chromosome and only one
mutant allele is required for expression of the phenotype in females)

5. Y-linked Inheritance (the locus is on the Y chromosome)

6. Mitochondrial inheritance (the locus is on the mitochondrial "chromosome").


Inheritance of Human traits –
1. Autosomal recessive inheritance (the locus is on an autosomal chromosome and
both alleles must be mutant alleles to express the phenotype)

Characteristics of autosomal recessive traits:


– For rare traits, most affected individuals have unaffected parents
– All children of affected parents are affected
– The risk of an affected child with heterozygous parents is 25%
– The trait is expressed in both males and females
Inheritance of Human traits –
2. Autosomal dominant inheritance (the locus is on an autosomal chromosome and
only one mutant allele is required for expression of the phenotype)
Characteristics of autosomal dominant traits:

– Heterozygotes have an abnormal phenotype


– Every affected individual has at least one affected parent (except in traits
with high mutation rates)
– If an affected individual is heterozygous and has an unaffected mate, each
child has a 50% chance of being affected
– Two affected individuals can have an unaffected child
– Usually an affected family member in each generation
The inheritance pattern of an
autosomal recessive disorder
with two carrier parents
reflects a 3:1 probability of
expression among offspring
The mother is a carrier and each son
The affected father passes the has a 50% chance of being affected.
STS mutation to his daughters, Each daughter has a 50% chance of
but his sons are unaffected. being a carrier.

The mother is a carrier and The affected father passes the STS
each son has a 50% chance of mutation to his daughters, but his
being affected. Each daughter sons are unaffected.
has a 50% chance of being a
carrier.
http://confettiskin.com/wp/2013/01/24/x-linked-ichthyosis/
Inheritance of Human traits –
3. X-linked recessive inheritance (the locus is on the X chromosome and both alleles
must be mutant alleles to express the phenotype in females)

Characteristics of X-linked recessive traits:

Affected males receive the mutant X-linked allele from their mother and
transmit it to all of their daughters, but not to their sons
– Daughters of affected males are usually heterozygous
– Sons of heterozygous females have a 50% chance of being affected
– Hemizygous males (only one X) and females homozygous for the allele are
affected.
Inheritance of Human traits –
4. X-linked dominant inheritance (the locus is on the X chromosome and only one
mutant allele is required for expression of the phenotype in females)

Characteristics of X-linked dominant traits:


Quite rare inheritance pattern

-- Affected males produce all affected daughters and no affected sons


-- A heterozygous affected female will transmit the trait to half of her children
-- Sons and daughters are equally affected
-- On average, twice as many daughters as sons are affected
Inheritance of Human traits –
5. Y-linked Inheritance / Paternal inheritance (the locus is on the Y chromosome)

Characteristics of Y-linked dominant traits:

Only males have Y chromosomes


– Genes on the Y chromosome are passed directly from father to son
-- All Y-linked genes are expressed
– Males are hemizygous for genes on the Y chromosome
-- To date only 36 Y-linked traits have been identified
•Examples: Azoospermia- the complete inability to produce sperm,
•Retinitis Pigmentosa- progressive loss of sight starting with decreased night
vision, followed by loss of peripheral or side vision and finally blindness
Inheritance of Human traits –
6. Mitochondrial inheritance (the locus is on the mitochondrial "chromosome").
Non-Mendelian Maternal inheritance

Mitochondria
–Cytoplasmic organelles that convert energy from food into ATP (ATP powers
cellular functions)
–Carry DNA for 37 mitochondrial genes
•Genetic disorders in mitochondrial DNA are associated with defects in energy
conversion
-- Mitochondria (and genetic disorders caused by mutations in mitochondrial
genes) are maternally inherited
•Mitochondria are transmitted from mothers to all their offspring through the
cytoplasm of the egg
Inheritance of Human traits – Brown Eyes
Eye color is inherited as a polygenic not as a
monogenic trait.

Human eye color


comes from melanocytes: cells which make
the brown pigment melanin.

Melanocytes are cells making melanin and


melanosomes are bodies in the cytoplasm
storing melanin. In the eye, melanin is not
made continuously like in skin and hair.

The peripupillary ring is shown on the right


and isn’t understood genetically yet.
• Eye color is a complete dominance
inheritance pattern:
• Brown is represented by B
• Blue is represented by b
• The genotype of a person with brown eyes
could be: BB or Bb
– One “B” from each parent and
– a second “B” or ‘b’ from each parent
http://www.biosci.ohio-state.edu/~pfuerst/courses/eeobmg640/reading1eyecolor.pdf
• The phenotype of BB or Bb is brown eyes
Inheritance of Human traits –Polydactyly Autosomal dominant inheritance

Polydactyly is an inherited condition in which a person has extra fingers or toes.

It is caused by a dominant allele of a gene. This means it can be passed on by


just one parent if they have the disorder.

The genetic diagram shows how this can happen.

Offspring need to carry just one dominant allele from their parents to inherit the
polydactyl condition
Inheritance of Human traits –Diabetes insipidus,
Diabetes insipidus characterized by inability to concentrate the urine, which
results in polyuria (excessive urine production) and polydipsia (excessive thirst).

Nephrogenic diabetes insipidus is a rare hereditary disorder, most commonly


transmitted in an X chromosome-linked recessive manner. characterized by the
lack of renal response to the action of antidiuretic hormone [Arg8]vasopressin.

Autosomal dominant familial neurohypophyseal diabetes insipidus (adFNDI) is a


form of diabetes insipidus caused by absence of circulating arginine vasopressin
(AVP).
Inheritance of Human traits –Phenylketonuria
Autosomal recessive inheritance

Phenylketonuria (PKU) is a prominent example


of a single-gene disease with an autosomal
recessive inheritance pattern.

PKU is associated with mutations in the gene


that encodes the enzyme phenylalanine
hydroxylase (PAH),

when a person has these mutations, he or she


cannot properly manufacture PAH, so he or
she is subsequently unable to break down
the amino acid phenylalanine, which is an
essential building block of dietary proteins.

As a result, individuals with PKU accumulate


high levels of phenylalanine in their urine and
blood, and this buildup eventually causes
mental retardation and behavioral
abnormalities.
Inheritance of Human traits – Sickle cell Anemia

Sickle cell disease is an autosomal recessive blood disorder that occurs in


approximately 1 in every 500 African-American births with a carrier frequency of
1/10. It is a disorder that is also prevalent among Mediterranean populations,
Puerto Ricans, and individuals from some South American and Arab countries.

Sickle cell disease is caused by one specific mutation in the beta-globin chain
gene resulting in a substitution of valine for glutamic acid at the sixth position
of the beta-globin chain.

This leads to abnormalities in the morphology of the red blood cell (sickling)
under conditions of low oxygen tension.

Ultimately, this abnormality leads to hemolysis and vaso-occlusion. Carriers of


sickle cell anemia usually are clinically normal, but they can be identified readily
by hemoglobin electrophoresis because the sickle hemoglobin (HbS) has a
different electrical charge compared with normal hemoglobin (HbA).

Carrier testing by hemoglobin electrophoresis is recommended for all African-


American women contemplating pregnancy to facilitate the identification of
carrier couples.
Genetic counselling

Genetic Counselling is a non-directive and non-judgmental communication process


that confidentially deals with the human problems associated with the
occurrence, or risk of occurrence of a genetic disorder in a family, and that
provides accurate scientific and comprehendible information so that families can
take their own decisions.

Genetic counseling may be described as the process through which individuals


affected by, or at risk for a problem which may be genetic or hereditary, are
informed of :
• The consequences of the disorder.
• The probability of suffering from or of transmitting it to their offspring,
• The potential means of treating or of avoiding the occurrence of the
malformation or disease in question.

Genetic counselling are of 2 types:

1. Prospective genetic counselling


2. Retrospective
Genetic counselling
Genetic counselling is the utilisation of knowledge of genetics to predict the probability
of genetic disorders. It is of 2 types:

Prospective genetic counselling


• In this the genetic disorder has not yet expressed itself
• It is done in heterozygotic individuals to assess the probability of having a child with
genetic disorders
• If a person is identified as heterozygotic for a genetic condition, he/she should be advised
against marrying another heterozygotic individual as there is increased risk of the trait
expressing itself in the phenotype

Retrospective genetic counselling


• In this, the disease has already occurred in the family
• This is more commonly done compared to prospective genetic counselling
• This is because, people usually come for genetic counselling only after having a child with
congenital anomalies / mental retardation / inborn errors of metabolism
• The interventions as a part of retrospective genetic counselling are:
• Contraception
• Sterilization
• Termination of pregnancy
Genetic counselling
Components of genetic counseling:

1. Interpretation of family and medical histories to assess the chance of disease


occurrence or recurrence

2. Education about inheritance, testing, management, prevention, resources and


research

3. Counseling to promote informed choices and adaptation to the risk or


condition

Areas of Practice
􀂄 Prenatal Genetics
􀂄 Pediatric Genetics
􀂄 Adult Genetics
􀂄 Cancer Genetics
􀂄 Metabolism Genetics
􀂄 Disease Research
􀂄 Diagnostic Laboratory
􀂄 Support Groups
􀂄 Public Health
􀂄 Government
Genetic counselling

When is genetic counseling provided?


1. Prenatal genetic counseling Mother 35+ years at delivery Abnormal prenatal
screening History of a known or suspected genetic disorder, birth defect or
chromosomal abnormality Exposure to known or suspected teratogen Mother
with medical condition that can affect fetal development Two or more pregnancy
losses Parents who are blood relatives Ethnic background related to higher risk.

2. Pediatric genetic counseling Abnormal newborn screening results Child with


one or more birth defects Child with abnormal growth Child with mental
retardation or developmental delay Blindness or deafness Known or suspected
genetic disorder or chromosome abnormality Family history of known or
suspected genetic disorder or chromosome abnormality

3. Adult genetic counseling Mental retardation History of hereditary cancers


History of known or suspected genetic condition Blindness or deafness
Development of a degenerative disease Pregnancy planning.
Genetic counselling

GENETIC COUNSELLING SESSION

1. Assessment: Gathering information

2. Evaluation: Interpreting medical and family history, results of physical


examination and tests.

3. Communication: Sharing information about the condition.

4. Support: Helping the family cope Follow-up Maintaining on-going


communication
Genetic counselling

GENETIC COUNSELLING SESSION

1. Assessment: Gathering information

2. Evaluation: Interpreting medical and family history, results of physical


examination and tests.

3. Communication: Sharing information about the condition.

4. Support: Helping the family cope Follow-up Maintaining on-going


communication
Eugenics

Eugenics, meaning "well born," was introduced in the 1880s by Sir Francis
Galton, a cousin of Charles Darwin and the father of modern statistics.
Galton pioneered the use of pedigrees, twin studies, and statistical
correlation for the purpose of using that knowledge to improve "the
breed of man.“

Positive eugenics
advocating the improvement of human genetic traits through the promotion of
higher reproduction of people with desired traits.

Negative eugenics
advocating the improvement of human genetic traits through the promotion
of reduced reproduction of people with less-desired or undesired traits
(negative eugenics).
summary

• Pedigrees are charts of family histories that show the phenotypes


and family relationships of the individuals. Pedigrees are basically
family trees that do not use names or words but instead use
symbols to convey information about the individuals and their
status in regards to a particular trait or condition.
• Patterns of Inheritance of human traits. Mendelian and non-
mendelian traits with their pedigree analysis.
• Bringing genetics to society. Genetic counselling and eugenics as
applications of human genetics to improve human race.
References
1. Bhamrah, H.S. and Kavita Juneja. “Molecular cell Biology”, Anmol publications Pvt.Ltd.
2. Gupta, P.K. (1996) “Genetics” Rastogi Publications.
3. Powar, C.B. (2003) “Genetics” Vol.I & Vol II.
4. Ranga, M.M. “Animal Biotechnology (Agrobios), Published by Agrobios (India).
5. Rastogi, Sharma, V.N. and Anuradha Tandon (1993). “Concepts in Molecular Biology”. Wiley
Eastern Ltd. N. Delhi.
6. Smustad, Simmons, Jenkins (1999). “Principles of Genetics” John Wiley and sons. Inc.
7. Daniel Fairbanks, W.Ralph Anderson. “Genetics, the continuity of life” (1999). Brooks/Cole
Publishing Company, New York.
8. Verma, P.S. & Agarwal V.K. (2004). “Cell Biology, Genetics, Molecular Biology, Evolutionary
Ecology”. S.Chand &Company, Pvt. Ltd. New Delhi.

http://www.ncbi.nlm.nih.gov/books/NBK21977/
http://www.ncbi.nlm.nih.gov/books/NBK7573/
http://www.ncbi.nlm.nih.gov/books/NBK22090/
http://www.ncbi.nlm.nih.gov/books/NBK22079/
http://www.genesinlife.org/genetics-101/how-does-genetics-work/main-inheritance-patterns
http://www.in.gov/isdh/26078.html
http://www.newbornscreening.info/Pro/genetics.html
http://www.uvm.edu/~cgep/Education/Inheritance2.html
Thank you

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