Patho Module 1- Genetics

Autosomal Dominant

Autosomal Dominant

Autosomal Dominant

Autosomal Dominant

Autosomal Recessive

Autosomal Recessive

Autosomal Recessive

Autosomal Recessive

X-Linked Dominant

X-Linked Dominant

X-Linked Dominant

X-Linked Recessive

X-Linked Recessive

X-Linked Recessive

100%

100%

Very variable. Even within the same family

the number and visual appearance of the chromosomes in the cell nuclei of an organism or species.

Single X chromosome

Trisomy of chromosome 21

1.Decreased intellect

2.Physical deformities (large tongue, wide set eyes)

3. Life limitting

1. Short Stature

2. Congenital heart disease

3. Ovarian Dysfunction

4. Life expectancy around 50 years

5. Higher incidence of learning disabilities but usually normal intellect

100%

As abnormal protein accumulates in neurons, it causes neurodegenerations. Result is progressive motor dysfunction and death. Usually in a schizophrenic state.

1. CAG and CGG common repeats

2. Number of repeats goes up with each generations

3 Higher number of repeats= earlier onset of diseases and increased severity of disease

4. Counseling often includes warnings against reproduction

1. Huntington Disease

2. Fragile X

Passed almost exclusively through maternal lines (eggs contain high number of mitochondria. Sperm contain almost none)

Leber Hereditary Optic Neuropathy (LHON)- results in vision loss at an early age

XXY

1. Tall stature

2. Long Arms

3. Sparce body hair

4. High voice

5. Normal life expectancy

one of two or more alternative forms of a gene that arise by mutation and are found at the same place on a chromosome. One allele is inherited from each parent

Having the same version of an allele, and having two different versions of the allele

GENES:

G-Groups of Anomalies are present. (things you don’t often see and multiple present)  

E-Early or extreme presentation  

N- Neurodevelopmental delay or neurogenerative diseases 

E-Exceptional Pathology (finding several different cancers simultaneously or finding in organs or structures of bilateral organs) 

S- Surprising Lab values (repeat to ensure) 

1. low protein and low phenylamine diet

2. otherwise or without detection, will lead to cognitive delays

3. Early intervention improves outcomes, including in the Newborn Screening

Only one gene is affected

Examples: Marfan syndrome and hereditary breast cancer

monogenetic disorder. single gene mutation of FBN1, is autosomal dominant but about 25% of cases are random mutation

Need a mutation of both BRCA1 and BRCA 2 (tumor suppressor genes)

results from combination of genetic, environmental and lifestyle. Often more than one gene contributes to genetic component. Examples: CAD and Major Depressive Disorder

Genetic alterations- alterations at the gene level

Epigenetic alterations- alterations in the expression of genes. Influenced by lifestyle and environmental factors (chemical exposure, drugs, aging, and diet)

1. Histone modification

2. DNA methylation

3. Non-coding DNA expression

1. Histone is responsible for how tight the DNA is wound.  By altering the winding of the DNA, it can become more accessible to target OR if tighter, decrease the likelihood of it replicating through transcription.  

2. Acetylation: makes gene more accessible vs deacetylation: decreases the likelihood of transcription.  

The addition of a Methyl group to the DNA sequence, stabilizes the DNA and reduces transcription rates. *like a sleeve. Slides over the genome and tells it to be quite.