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GENETICS

Sarmishtha Ghosh

Lecture- GEN 2Dated: 2nd , January, 2013


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Inheritance Patternand Pedigree


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Learning Objectives

• Heredity - meaning

• Inheritance patterns – Mendelian inheritance

– Non mendelian inheritance

• Autosomal and Sex linked Traits

• Dominant & recessive traits

• Transmision of traits and factors determining it.

• Genetic VariationSLIDES # 4-12 GENERAL UNDERSTANDING

AND CONCEPT


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specialty of medicine that involves

the diagnosis and management of

hereditary disorders

field of scientific research that may or

may not apply to medicine, but medical

genetics refers to the application of

genetics to medical care.

research on the causes and inheritance of genetic

disorders would be considered within both human

genetics and medical genetics,

the diagnosis, management, and counseling of individuals withgenetic disorders would be considered part of medical genetics.

the study of typically non-medical phenotypes such as the genetics of

eye color would be considered part of human genetics, but not

necessarily relevant to medical genetics (except in situations such as

albinism).

http://en.wikipedia.org/wiki/Medicinehttp://en.wikipedia.org/wiki/Hereditary_disorderhttp://en.wikipedia.org/wiki/Genetic_disordershttp://en.wikipedia.org/wiki/Genetic_disordershttp://en.wikipedia.org/wiki/Phenotypehttp://en.wikipedia.org/wiki/Albinismhttp://en.wikipedia.org/wiki/Albinismhttp://en.wikipedia.org/wiki/Phenotypehttp://en.wikipedia.org/wiki/Genetic_disordershttp://en.wikipedia.org/wiki/Genetic_disordershttp://en.wikipedia.org/wiki/Hereditary_disorderhttp://en.wikipedia.org/wiki/Medicine


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– Prenatal Genetics

• 1970s - Prenatal Ultrasound & Amniocentesis – Inheritance of Genetically Complex Disorders

• Non-Mendelian Genetics – Genomic Imprinting

– Triple Nucleotide Repeats

– Mitochondrial Inheritance

• 1990s - Neuropsychiatric Disorders, Diabetes, Cardiovascular

– Interaction of genes with environmental triggers

Medical Genetics: 1960sto the present

– DNA Genetics

•1953 - Watson and Crick’s Double Helix

•1992 – 2003 Human Genome Project

•2003 -> the future of medical Dx & Rx


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http://ocw.tufts.edu/Content/20/lecturenotes/301642/301658


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is a newer term

for medical genetics

incorporates areas such asgene therapy, personalized

medicine, and the rapidlyemerging new medical

specialty, predictive medicine.

http://en.wikipedia.org/wiki/Gene_therapyhttp://en.wikipedia.org/wiki/Personalized_medicinehttp://en.wikipedia.org/wiki/Personalized_medicinehttp://en.wikipedia.org/wiki/Predictive_medicinehttp://en.wikipedia.org/wiki/Predictive_medicinehttp://en.wikipedia.org/wiki/Personalized_medicinehttp://en.wikipedia.org/wiki/Personalized_medicinehttp://en.wikipedia.org/wiki/Gene_therapy


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Clinical genetics is the practice of clinical medicine with particular attention tohereditary disorders. Referrals are made to genetics clinics for a variety ofreasons, including birth defects, developmental delay, autism, epilepsy, short

stature, and many others. Examples of genetic syndromes that are commonlyseen in the genetics clinic include chromosomal rearrangements, Downsyndrome, DiGeorge syndrome (22q11.2 Deletion Syndrome), Fragile Xsyndrome, Marfan syndrome, Neurofibromatosis, Turner syndrome, andWilliams syndrome.

Genetic counseling is the

process through which a

genetic counselor

provides informationabout genetic conditions,

diagnostic testing, and

risks in other family

members, within the

framework of nondirective

counseling.

•Metabolic (or biochemical) geneticsinvolves the diagnosis and management ofinborn errors of metabolism in which patients

have enzymatic deficiencies that perturbbiochemical pathways involved inmetabolism of carbohydrates, amino acids,and lipids. Examples of metabolic disordersinclude galactosemia, glycogen storagedisease, lysosomal storage disorders,metabolic acidosis, peroxisomal disorders,phenylketonuria, and urea cycle disorders.

http://en.wikipedia.org/wiki/Hereditary_disorderhttp://en.wikipedia.org/wiki/Birth_defectshttp://en.wikipedia.org/wiki/Developmental_delayhttp://en.wikipedia.org/wiki/Autismhttp://en.wikipedia.org/wiki/Epilepsyhttp://en.wikipedia.org/wiki/Short_staturehttp://en.wikipedia.org/wiki/Short_staturehttp://en.wikipedia.org/wiki/Chromosome_abnormalityhttp://en.wikipedia.org/wiki/Down_syndromehttp://en.wikipedia.org/wiki/Down_syndromehttp://en.wikipedia.org/wiki/DiGeorge_syndromehttp://en.wikipedia.org/wiki/Fragile_X_syndromehttp://en.wikipedia.org/wiki/Fragile_X_syndromehttp://en.wikipedia.org/wiki/Marfan_syndromehttp://en.wikipedia.org/wiki/Neurofibromatosishttp://en.wikipedia.org/wiki/Turner_syndromehttp://en.wikipedia.org/wiki/Williams_syndromehttp://en.wikipedia.org/wiki/Genetic_counselorhttp://en.wikipedia.org/wiki/Inborn_errors_of_metabolismhttp://en.wikipedia.org/wiki/Biochemistryhttp://en.wikipedia.org/wiki/Carbohydrateshttp://en.wikipedia.org/wiki/Amino_acidshttp://en.wikipedia.org/wiki/Lipidshttp://en.wikipedia.org/wiki/Galactosemiahttp://en.wikipedia.org/wiki/Glycogen_storage_diseasehttp://en.wikipedia.org/wiki/Glycogen_storage_diseasehttp://en.wikipedia.org/wiki/Lysosomal_storage_disorderhttp://en.wikipedia.org/wiki/Metabolic_acidosishttp://en.wikipedia.org/wiki/Peroxisomal_disordershttp://en.wikipedia.org/wiki/Phenylketonuriahttp://en.wikipedia.org/wiki/Urea_cycle_disorderhttp://en.wikipedia.org/wiki/Urea_cycle_disorderhttp://en.wikipedia.org/wiki/Phenylketonuriahttp://en.wikipedia.org/wiki/Peroxisomal_disordershttp://en.wikipedia.org/wiki/Metabolic_acidosishttp://en.wikipedia.org/wiki/Lysosomal_storage_disorderhttp://en.wikipedia.org/wiki/Glycogen_storage_diseasehttp://en.wikipedia.org/wiki/Glycogen_storage_diseasehttp://en.wikipedia.org/wiki/Galactosemiahttp://en.wikipedia.org/wiki/Lipidshttp://en.wikipedia.org/wiki/Amino_acidshttp://en.wikipedia.org/wiki/Carbohydrateshttp://en.wikipedia.org/wiki/Biochemistryhttp://en.wikipedia.org/wiki/Inborn_errors_of_metabolismhttp://en.wikipedia.org/wiki/Genetic_counselorhttp://en.wikipedia.org/wiki/Williams_syndromehttp://en.wikipedia.org/wiki/Turner_syndromehttp://en.wikipedia.org/wiki/Neurofibromatosishttp://en.wikipedia.org/wiki/Marfan_syndromehttp://en.wikipedia.org/wiki/Fragile_X_syndromehttp://en.wikipedia.org/wiki/Fragile_X_syndromehttp://en.wikipedia.org/wiki/DiGeorge_syndromehttp://en.wikipedia.org/wiki/Down_syndromehttp://en.wikipedia.org/wiki/Down_syndromehttp://en.wikipedia.org/wiki/Chromosome_abnormalityhttp://en.wikipedia.org/wiki/Short_staturehttp://en.wikipedia.org/wiki/Short_staturehttp://en.wikipedia.org/wiki/Epilepsyhttp://en.wikipedia.org/wiki/Autismhttp://en.wikipedia.org/wiki/Developmental_delayhttp://en.wikipedia.org/wiki/Birth_defectshttp://en.wikipedia.org/wiki/Hereditary_disorder


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Mitochondrial genetics

• Mitochondrial genetics concerns thediagnosis and management of

mitochondrial disorders, which have amolecular basis but often result inbiochemical abnormalities due todeficient energy production.

There exists some overlap betweenmedical genetic diagnostic laboratoriesand molecular pathology.

Cytogenetics

• Cytogenetics is the study ofchromosomes and chromosomeabnormalities. While cytogeneticshistorically relied on microscopy to

analyze chromosomes, new moleculartechnologies such as array comparativegenomic hybridization are nowbecoming widely used.

• Examples of chromosome abnormalitiesinclude aneuploidy, chromosomalrearrangements, and genomicdeletion/duplication disorders

Molecular genetics

• Molecular genetics involves thediscover y of and laboratory testingfor DNA mutations that underliemany single gene disorders.

• Examples of single gene disordersinclude achondroplasia, cysticfibrosis, Duchenne muscular dystrophy, hereditary breastcancer (BRCA1/2), Huntingtondisease, Marfan syndrome,Noonan syndrome, and Rettsyndrome.

• Molecular tests are also used inthe diagnosis of syndromesinvolving epigenetic abnormalities,such as Angelman syndrome,Beckwith-Wiedemann syndrome,Prader-willi syndrome, anduniparental disomy.

http://en.wikipedia.org/wiki/Mitochondrialhttp://en.wikipedia.org/wiki/Molecular_pathologyhttp://en.wikipedia.org/wiki/Chromosome_abnormalitieshttp://en.wikipedia.org/wiki/Chromosomeshttp://en.wikipedia.org/wiki/Chromosome_abnormalitieshttp://en.wikipedia.org/wiki/Chromosome_abnormalitieshttp://en.wikipedia.org/wiki/Microscopyhttp://en.wikipedia.org/wiki/Array_comparative_genomic_hybridizationhttp://en.wikipedia.org/wiki/Array_comparative_genomic_hybridizationhttp://en.wikipedia.org/wiki/Array_comparative_genomic_hybridizationhttp://en.wikipedia.org/wiki/Array_comparative_genomic_hybridizationhttp://en.wikipedia.org/wiki/Chromosome_abnormalityhttp://en.wikipedia.org/wiki/Chromosome_abnormalityhttp://en.wikipedia.org/wiki/Aneuploidyhttp://en.wikipedia.org/wiki/Chromosome_abnormalityhttp://en.wikipedia.org/wiki/Chromosome_abnormalityhttp://en.wikipedia.org/wiki/DNAhttp://en.wikipedia.org/wiki/DNAhttp://en.wikipedia.org/wiki/Genetic_disordershttp://en.wikipedia.org/wiki/Achondroplasiahttp://en.wikipedia.org/wiki/Cystic_fibrosishttp://en.wikipedia.org/wiki/Duchenne_muscular_dystrophyhttp://en.wikipedia.org/wiki/Duchenne_muscular_dystrophyhttp://en.wikipedia.org/wiki/Duchenne_muscular_dystrophyhttp://en.wikipedia.org/wiki/Breast_cancerhttp://en.wikipedia.org/wiki/Duchenne_muscular_dystrophyhttp://en.wikipedia.org/wiki/Duchenne_muscular_dystrophyhttp://en.wikipedia.org/wiki/Breast_cancerhttp://en.wikipedia.org/wiki/Breast_cancerhttp://en.wikipedia.org/wiki/Huntington_diseasehttp://en.wikipedia.org/wiki/Noonan_syndromehttp://en.wikipedia.org/wiki/Noonan_syndromehttp://en.wikipedia.org/wiki/Noonan_syndromehttp://en.wikipedia.org/wiki/Marfan_syndromehttp://en.wikipedia.org/wiki/Rett_syndromehttp://en.wikipedia.org/wiki/Rett_syndromehttp://en.wikipedia.org/wiki/Noonan_syndromehttp://en.wikipedia.org/wiki/Rett_syndromehttp://en.wikipedia.org/wiki/Rett_syndromehttp://en.wikipedia.org/wiki/Rett_syndromehttp://en.wikipedia.org/wiki/Angelman_syndromehttp://en.wikipedia.org/wiki/Angelman_syndromehttp://en.wikipedia.org/wiki/Angelman_syndromehttp://en.wikipedia.org/wiki/Angelman_syndromehttp://en.wikipedia.org/wiki/Beckwith-Wiedemann_syndromehttp://en.wikipedia.org/wiki/Uniparental_disomyhttp://en.wikipedia.org/wiki/Prader-willi_syndromehttp://en.wikipedia.org/wiki/Uniparental_disomyhttp://en.wikipedia.org/wiki/Uniparental_disomyhttp://en.wikipedia.org/wiki/Uniparental_disomyhttp://en.wikipedia.org/wiki/Uniparental_disomyhttp://en.wikipedia.org/wiki/Prader-willi_syndromehttp://en.wikipedia.org/wiki/Prader-willi_syndromehttp://en.wikipedia.org/wiki/Prader-willi_syndromehttp://en.wikipedia.org/wiki/Prader-willi_syndromehttp://en.wikipedia.org/wiki/Prader-willi_syndromehttp://en.wikipedia.org/wiki/Beckwith-Wiedemann_syndromehttp://en.wikipedia.org/wiki/Beckwith-Wiedemann_syndromehttp://en.wikipedia.org/wiki/Beckwith-Wiedemann_syndromehttp://en.wikipedia.org/wiki/Beckwith-Wiedemann_syndromehttp://en.wikipedia.org/wiki/Beckwith-Wiedemann_syndromehttp://en.wikipedia.org/wiki/Angelman_syndromehttp://en.wikipedia.org/wiki/Angelman_syndromehttp://en.wikipedia.org/wiki/Angelman_syndromehttp://en.wikipedia.org/wiki/Epigenetichttp://en.wikipedia.org/wiki/Rett_syndromehttp://en.wikipedia.org/wiki/Rett_syndromehttp://en.wikipedia.org/wiki/Rett_syndromehttp://en.wikipedia.org/wiki/Noonan_syndromehttp://en.wikipedia.org/wiki/Marfan_syndromehttp://en.wikipedia.org/wiki/Marfan_syndromehttp://en.wikipedia.org/wiki/Marfan_syndromehttp://en.wikipedia.org/wiki/Huntington_diseasehttp://en.wikipedia.org/wiki/Huntington_diseasehttp://en.wikipedia.org/wiki/Breast_cancerhttp://en.wikipedia.org/wiki/Breast_cancerhttp://en.wikipedia.org/wiki/Duchenne_muscular_dystrophyhttp://en.wikipedia.org/wiki/Duchenne_muscular_dystrophyhttp://en.wikipedia.org/wiki/Duchenne_muscular_dystrophyhttp://en.wikipedia.org/wiki/Duchenne_muscular_dystrophyhttp://en.wikipedia.org/wiki/Cystic_fibrosishttp://en.wikipedia.org/wiki/Cystic_fibrosishttp://en.wikipedia.org/wiki/Achondroplasiahttp://en.wikipedia.org/wiki/Genetic_disordershttp://en.wikipedia.org/wiki/DNAhttp://en.wikipedia.org/wiki/Chromosome_abnormalityhttp://en.wikipedia.org/wiki/Chromosome_abnormalityhttp://en.wikipedia.org/wiki/Aneuploidyhttp://en.wikipedia.org/wiki/Array_comparative_genomic_hybridizationhttp://en.wikipedia.org/wiki/Array_comparative_genomic_hybridizationhttp://en.wikipedia.org/wiki/Microscopyhttp://en.wikipedia.org/wiki/Chromosome_abnormalitieshttp://en.wikipedia.org/wiki/Chromosome_abnormalitieshttp://en.wikipedia.org/wiki/Chromosomeshttp://en.wikipedia.org/wiki/Molecular_pathologyhttp://en.wikipedia.org/wiki/Mitochondrial


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Reasons Why Medical Genetics Hasn’tLived Up to the Predictions

Physicians are uncomfortable with basic genetics

Primary care physicians don’t have time for genetics

Genetics of the “common disorders” hasn’t reached

the stage where it is useful

susceptibility genes have a low predictive value

Patients aren’t ready for genetic testing

Issues of screening and presymptomatic testing arevery complex


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DNA molecules are large and complex.

They carry the genetic code that determines

the characteristics of a living thing.

Except for identical twins, each person’s

DNA is unique. This is why people can be

identified using DNA fingerprinting. DNA canbe cut up and separated, forming a sort of

'bar code' that is different from one person

to the next.

A short section of DNA which codes for

a specific protein by specifying the order

in which amino acids must be joined

together.

Chormosomes= single continuous

DNA double helix

46 DNA molecules > 6 billion

nucleotidesComplexed with several

chromosomal proteins


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Chromosomes

• consist of a single moleculeof DNA associated with: – many copies of 5 kinds of

histones.• Histones are proteins rich in

lysine and arginine residuesand thus positively-charged.

• they bind tightly to thenegatively-charged phosphates in DNA.

– a small number of copies ofmany different kinds of non-

histone proteins.• Most of these are transcription

factors that regulate whichparts of the DNA will betranscribed into RNA

http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/N/Nucleus.htmlhttp://users.rcn.com/jkimball.ma.ultranet/BiologyPages/L/Lys_arg.gifhttp://users.rcn.com/jkimball.ma.ultranet/BiologyPages/L/Lys_arg.gifhttp://users.rcn.com/jkimball.ma.ultranet/BiologyPages/P/Phosphate.gifhttp://users.rcn.com/jkimball.ma.ultranet/BiologyPages/N/Nucleus.htmlhttp://users.rcn.com/jkimball.ma.ultranet/BiologyPages/N/Nucleus.htmlhttp://users.rcn.com/jkimball.ma.ultranet/BiologyPages/T/T.htmlhttp://users.rcn.com/jkimball.ma.ultranet/BiologyPages/T/T.htmlhttp://users.rcn.com/jkimball.ma.ultranet/BiologyPages/T/Transcription.htmlhttp://users.rcn.com/jkimball.ma.ultranet/BiologyPages/T/Transcription.htmlhttp://users.rcn.com/jkimball.ma.ultranet/BiologyPages/T/T.htmlhttp://users.rcn.com/jkimball.ma.ultranet/BiologyPages/T/T.htmlhttp://users.rcn.com/jkimball.ma.ultranet/BiologyPages/N/Nucleus.htmlhttp://users.rcn.com/jkimball.ma.ultranet/BiologyPages/N/Nucleus.htmlhttp://users.rcn.com/jkimball.ma.ultranet/BiologyPages/N/Nucleus.htmlhttp://users.rcn.com/jkimball.ma.ultranet/BiologyPages/P/Phosphate.gifhttp://users.rcn.com/jkimball.ma.ultranet/BiologyPages/L/Lys_arg.gifhttp://users.rcn.com/jkimball.ma.ultranet/BiologyPages/L/Lys_arg.gifhttp://users.rcn.com/jkimball.ma.ultranet/BiologyPages/N/Nucleus.html


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Heredity

• The transfer of characteristics fromparent to offspring through genes.

• A gene, the “unit of heredity,” is madeof deoxyribonucleic acid (DNA).

• There are many genes on eachmolecule of DNA.


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How Are Features Passed Along


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First experimental evidence that DNAtransmits genetic information.

AVERY, MACLEOD, MCCARTY 1944

-- Using an x-ray pattern of DNAgenerated by Rosalind Franklin, MauriceWilkins, James Watson and Francis Crick

publish their double-helix model DNA.

1953

FRANKLIN, WATSON, CRICK, WILKINS

1962 -- Wilkins, Watson & Crick win Nobel Prize

Protein synthesis describedThey decipher the genetic code that all

living cells use to translate the series of

bases in their DNA into instructions for the

production of proteins.

NIRENBERG & KHORANA 1960-1966


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Chimp 48

Orangutan 48

Gorilla 48

Gibbons 44

Green Monkey 60

Baboon 42

Owl Monkey 54

Squirrel Monkey 44

Ringtailed Lemur 56

Black Lemur 44


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GLOSSARY

• GENE

• CHROMOSOME

• LOCUS

• DIPLOID AND HAPLOID

• HOMOZYGOUS

• HETEROZYGOUS

• DOMINANT

• RECESSIVE

• GENOTYPE

• PHENOTYPE

GENDER

SEX

Gender is a range of characteristics

used to distinguish between males and

females, particularly in the cases of

men and women and the masculine

and feminine attributes assigned tothem.

Sex is a process of combining and mixing

genetic traits, often resulting in the

specialization of organisms into a male or

female variety (each known as a sex).

http://en.wikipedia.org/wiki/Malehttp://en.wikipedia.org/wiki/Femalehttp://en.wikipedia.org/wiki/Menhttp://en.wikipedia.org/wiki/Womenhttp://en.wikipedia.org/wiki/Masculinityhttp://en.wikipedia.org/wiki/Femininityhttp://en.wikipedia.org/wiki/Geneticshttp://en.wikipedia.org/wiki/Organismhttp://en.wikipedia.org/wiki/Malehttp://en.wikipedia.org/wiki/Femalehttp://en.wikipedia.org/wiki/Femalehttp://en.wikipedia.org/wiki/Malehttp://en.wikipedia.org/wiki/Organismhttp://en.wikipedia.org/wiki/Geneticshttp://en.wikipedia.org/wiki/Femininityhttp://en.wikipedia.org/wiki/Masculinityhttp://en.wikipedia.org/wiki/Womenhttp://en.wikipedia.org/wiki/Menhttp://en.wikipedia.org/wiki/Femalehttp://en.wikipedia.org/wiki/Male


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Sex and gender

• Sex refers to

biologicaldifferences;chromosomes,

hormonal profiles,internal andexternal sexorgans.

Gender describesthe characteristics

that a society or

culture delineates

as masculine or

feminine.


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• Variations of a gene -one set ofalleles (genes) from one parent andthe other set of alleles from the other

parent.• Some of the traits are based on

simple inheritance where one versionof a gene (dominant allele) masks the

expression of the other version of thatgene (recessive allele).

• Dominant allele = P; Recessiveallele = p


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Homozygous and Heterozygous

• A pair of identical alleles for a character , (PP,

pp); homozygous for that characteristic

• Two different alleles for a gene (Pp) -the

heterozygous condition for a characteristic


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all of your genes

INSTRUCTIONS

TRAITS / PHYSICAL

CHARACTERISTICS


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Mendel’s

experiments….

• 1865 -The principles of heredity written byGregor Johann Mendel

• Three important conclusions1. the inheritance of each trait is determined by

"units" or "factors" that are passed on todescendents unchanged (these units are nowcalled genes)

2. an individual inherits one such unit from eachparent for each trait

3. a trait may not show up in an individual but canstill be passed on to the next generation.

1822-1884

http://anthro.palomar.edu/mendel/glossary.htmhttp://anthro.palomar.edu/mendel/glossary.htm


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Mendel’s Laws….

Law of Segregation (The "First Law")

• when any individual produces gametes, the

copies of a gene separate, so that each gamete

receives only one copy.

• A gamete will receive one copy or the other.

•

• The direct proof of this was later found when the

process of meiosis came to be known.

http://en.wikipedia.org/wiki/Meiosishttp://en.wikipedia.org/wiki/Meiosis


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The Second Law

Law of Independent Assortment (The "Second Law")

• copies of different genes assort independently of oneanother during gamete formation.

• One trait always resulted in a 3:1 ratio between dominantand recessive phenotypes,

• Two traits (dihybrid cross) showed 9:3:3:1 ratios

• • Different traits are inherited independently of each other,

so that there is no relation, for example, between a cat'scolor and tail length. This is actually only true forgenes that are not linked to each other.

http://en.wikipedia.org/wiki/Genetic_linkagehttp://en.wikipedia.org/wiki/Genetic_linkage


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Linked genes

• When looking back at dihybrid crosses, wehave only considering each gene separate,giving us a 9:3:3:1 ratio.

– When genes are studied on the samechromosome, they are referred to aslinked genes and note that the ratio is

only 3:1

– Notice how a linked-gene punnett isdifferent from a dihybrid.


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Inheritance patterns

• Inheritance patterns trace the transmission

of genetically encoded traits, conditions or

diseases to offspring.• There are several modes of inheritance:

• Single Gene or Mendelian

• Multifactorial

• Mitochondrial


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• Genetic conditions caused by a mutation

in a single gene follow predictable patterns

of inheritance within families.

• Single gene inheritance is also referred

to as Mendelian inheritance as they followtransmission patterns he observed in his

research on peas.


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Mendelian inheritance

• There are four types of patterns:

Autosomal dominant

Autosomal recessive

X-linked recessive

X-linked dominant


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• Autosomal: the gene responsible for the phenotype is

located on one of the 22 pairs of autosomes (non-sexdetermining chromosomes).

• X-linked: the gene that encodes for the trait is locatedon the X chromosome.

• Dominant: conditions that are manifest inheterozygotes (individuals with just one copy of themutant allele).

• Recessive: conditions are only manifest in individualswho have two copies of the mutant allele (arehomozygous).


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Pedigree

• A pedigree is a diagram of a family historythat shows relationships between family

members and their status with respect to a

particular hereditary condition.

• The index case, or affected person

through which the pedigree is discovered,is called the proband and is indicated by

an arrow on pedigrees.

U ff t d l S t


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Unaffected male Spontaneousabortion

Unaffected female Termination ofPregnancy

Affected male Pregnancy

Affected female Monozygotic twins

Deceased

unaffected male

Dizygotic twins

Deceased

unaffected femaleProband

Carrier male

Infertility

Carrier female

Sex not specified

P


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Autosomal Dominant

• Dominant conditions are expressed in

individuals who have just one copy of the mutantallele.

• The pedigree on the right illustrates thetransmission of an autosomal dominant trait.

• Affected males and females have an equalprobability of passing on the trait to offspring.

• Affected individual's have one normal copy ofthe gene and one mutant copy of the gene, thuseach offspring has a 50% chance on inheritingthe mutant allele.

• As shown in the next pedigree, approximatelyhalf of the children of affected parents inherit thecondition and half do not.


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Autosomal Dominant Conditions:

• Huntington Disease

• Acondroplasia (short-limbed dwarfism)

• polycystic kidney disease


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Autosomal Recessive

• Recessive conditions are clinically manifest onlywhen an individual has two copies of the mutantallele.

• When just one copy of the mutant allele ispresent, an individual is a carrier of the mutation,but does not develop the condition.

• Females and males are affected equally by traitstransmitted by autosomal recessive inheritance.

• When two carriers mate, each child has a 25%chance of being homozygous wild-type(unaffected); a 25% chance of being homozygousmutant (affected); or a 50% chance of beingheterozygous (unaffected carrier).


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Autosomal Recessive


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Autosomal Recessive

• Affected individuals are indicated bysolid black symbols and unaffectedcarriers are indicated by the half black

symbols.• Autosomal recessive diseases:

• Cystic fibrosis• Tay-Sachs• Hemochromatosis• Phenylketonuria (PKU)

X-linked Recessive


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X-linked Recessive

• X-linked recessive traits are not clinically manifest when

there is one normal copy of the gene.• All X-linked recessive traits are fully evident in malesbecause they only have one copy of the X chromosome,thus do not have a normal copy of the gene tocompensate for the mutant copy.

• For that same reason, women are rarely affected by X-linked recessive diseases, however they are affectedwhen they have two copies of the mutant allele.

• Because the gene is on the X chromosome there is nofather to son transmission, but there is father todaughter; and mother to daughter and son transmission.

• If a man is affected with an X-linked recessive condition,all his daughter will inherit one copy of the mutant allelefrom him.


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X-linked Recessive

• X-linked Recessive Disorders:

• Duchenne muscular dystrophy

• hemophilia A

• X-linked severe combined immunedisorder (SCID)

• some forms of congenital deafness


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X-linked Recessive

X li k d D i t


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X-linked Dominant

• Because the gene is located on the X

chromosome, there is no transmission from

father to son, but there can be transmission from

father to daughter (all daughters of an affected

male will be affected since the father has onlyone X chromosome to transmit).

• Children of an affected woman have a 50%

chance of inheriting the X chromosome with the

mutant allele.• X-linked dominant disorders are clinically

manifest when only one copy of the mutant allele

is present.

X li k d D i t


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X-linked Dominant

• X-linked Dominant Disorders

• some forms of retinitis pigmentosa

• Chondrodysplasia Punctata

• Hypophosphatemic rickets

X li k d D i t


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X-linked Dominant


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• Genes on the autosomal chromosomes (1 through 22) areinherited in pairs, one from each parent.

• An autosomal recessive disorder occurs when both genes

of a pair are abnormal.

• Everyone carr ies a certain number of abnormalrecessive genes, usual ly as a single copy.

•

• In most cases, it is not until after the birth of a child with arecessive genetic condition that a couple is identified ascarriers with a 25% recurrence risk in future offspring ofeither sex.

• An autosomal dominant disorder is caused by a singleabnormal gene.

• Individuals who carry a dominant gene will usually showsigns of the disorder.

• They have a 50% occurrence risk in future offspring of either

sex.


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Multifactorial inheritance

• Most diseases have multifactorial inheritancepatterns.

• As the name implies, multifactorial conditionsare not caused by a single gene, but rather are aresult of interplay between genetic factors

and environmental factors.• Diseases with multifactorial inheritance are not

genetically determined, but rather a geneticmutation may predispose an individual to adisease.

• Other genetic and environmental factorscontribute to whether or not the diseasedevelops.


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• Numerous genetic alterations may predisposeindividuals to the same disease (geneticheterogeneity).

• For instance coronary heart disease risk factorsinclude high blood pressure, diabetes, andhyperlipidemia.

• All of those risk factors have their own geneticand environmental components.

• Thus multifactorial inheritance is far morecomplex than Mendelian inheritance and ismore difficult to trace through pedigrees.


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• Conditions with :• Alzheimers disease

• heart disease

• some cancers

• neural tube defects• schizophrenia

• insulin-dependent diabetes mellitus

• intelligence

• Some of the factors which contribute to the

development of breast cancer


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Mitochondrial inheritance

• Mitochondria are organelles found in the

cytoplasm of cells.

• Mitochondria are unique in that they have

multiple copies of a circular chromosome.

• Mitochondria are only inherited from the

mother's egg, thus only females can

transmit the trait to offspring, however they

pass it on to all of their offspring.


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Mitochondrial inheritance

• The primary function of mitochondria isconversion of molecule into usable energy.

• Thus many diseases transmitted by

mitochondrial inheritance affect organswith high-energy use such as the heart,

skeletal muscle, liver, and kidneys.

• Duchnne muscular dystropy• Beker’s muscular dystropy


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Simple Inheritance of Traitsthat Show Complete

Dominance


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Most people place their left thumb on top of


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Most people place their left thumb on top of

their right and this happens to be the

dominant phenotype.

Now, for fun, try clasping your hands so that

the opposite thumb is on top. Feels strange

and unnatural, doesn’t it? Alleles: L,l

Dominant phenotype: left thumb on top

Dominant genotype: L –

Recessive genotype: ll

A dominant allele causes the last joint of the

little finger to dramatically bend inward

toward the 4th finger. Lay both hands flat on

a table relax your muscles, and notewhether your have a bent or straight little

finger.

Alleles: B, b

Dominant phenotype: bent little finger

Dominant genotype: B –

Recessive genotype: bb


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Continued …….

9th January, 2013

@8-00 AM

lec gen1 sg2012batch4 - copy

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