Intro to Human Genetics EXAM 1

what is medical genetics

all diseases other than those caused by trauma, have a genetic component

most genetic diseases are rare

• cystic fibrosis 1/2000

• trisomy 21 1/800

• 50-60 % all spontaneous abortions due to chromosomal abnormalities

• 5% all newborns have a birth defect

at least 3000 disorders are known to be inherited by

transmission of a single gene mutation

in patient pediatric disease

71% have a major genetic component

97% of chronic disorders of childhood are genetically dtd

what childhood disorders are genetical determined

• cystic fibrosis

• hemoglobin

• sickle cell

• epilepsy

• autism

• congenital heart disease

• cleft lip

• chromosomal abnormalities

• cancer

infant mortality- what is leading cause

congenital malformations/anomalies at 20%

summary of medical genetics

• Inherited genetic influences ( mom and dad)

• 1st trimester: organogenesis - New mutations, chromosomal abnormalities

• 2 & 3 trimester” growth and development - External Influences ( FAS)

• childhood: growth and development

• adulthood

4 questions to ask in clinical genetics and genetic counseling

1. what is wrong? DIAGNOSIS

2. What is going to happen? PROGNOSIS

3. Why did it happen? Inheritance? PREVENTION

4. What can be done about it? TREATMENT

What do we do in medical genetics

• Clinical phenotype: medical probs, clinical testing

• genetic testing : biochemical. cytogenetics, molecular genetics ( sequencing)

• medical therapy : diet, enzyme replacement, gene therapy

• fam history

what are the genetic influences in disease

1. mendelian inheritance

2. chromosomal aneuploidies

3. multifactorarial

4. non mendelian single gene defect

mendelian inheritance

single gene disorders:

• autosomal recessibve ex: PKU, CF

• autosomal dominant ex: neurofibromatosis , achondroplasia

• X linked disorders: hemophilia A

chromosomal aneuploidies

• numerical - trisomy 21, 45X ( Turners)

• Structural rearrgangments ( Philadelphia chromosome)

Multifactorial inheritance

gene + environment

ex: isolated cleft lip/palate isolated congenital heart disease

Non menedelian single gene defects

trinucleotide repeats ( Fragile X, Hutingtons’s, myotonic dystrophy)

Mitochondrial ( comes from ovum so from mom) aka MERF

Myotonic Dystrophy

Trinucleotide (CTG)nn repeat disorder repeat disorder

normal CTG repeats: <35normal CTG repeats: <35

premutation carrier: 35-50premutation carrier: 35-50

mother’s 2 allele repeats: 29/327mother’s 2 allele repeats: 29/327

patient’s 2 allele repeats: 5/1200patient’s 2 allele repeats: 5/1200

• Progressive muscle weaknessProgressive muscle weakness

Cardiac arythmiasCardiac arythmias

Non mendelian genetic disorders

malformations may develop in u in utero which result from spontaneous

events upon gene

•• Teratogens (ETOH/medications

•• oligohydramnios - renal agenesisoligohydramnios s

• new mutations may occur within gametes which cause dominantly expressing disorders which neither parent expresses

•• achondroplasiaachondroplasia

• spontaneous chromosome rearrangements may occur in gametes or

fertilized ovum

•• free trisomy 21 (Down Syndrome)

FAS affects how many live births and traits

0.5-3/1000

• micrcephaly

• long plain philtrum

• thin upper lip

major consequences of FAS

developmental delay - IQ deficits

behavioral disturbances - attention deficits

growth retardation - intrauterine/postnatal

Intermittent binge drinking or daily moderate alcohol use can lead to FAS

Mechanisms: impairment of lipid rafts and function of cellular morphogens (signalling proteins)

non mendelian genetic factors

mobile elements in genome

• sequence in genome that duplicate and jump to the parts of genome- when they interact w a coding region→ problem. can inactivate

Epigenetics - nonsequence variation in genome

• Effects of modification of the genome without changes in DNA sequences (e.g., methylation of cytosine > thymidine)

• DNA Methylation silences genes; inactivates X chromosome in females

• Histone acetylation can affect transcription of genes

• May be inherited but not in Mendelian fashion

1S summary

• All that is genetic is not inherited

• Genetic susceptibilities can have multiple factors which must reach some threshold before clinical expression occurs

• Variability in expression is common and is influenced by environment

Genetic effects from

• nucleotide sequence changes

• epigenetic changes

• chromosomal deletion/duplication/translocation

• changes in gene expression from environment or genetic