9. Pedigrees and Genetic Diseases

What is a pedigree in genetics?

A pedigree traces a genetic trait through several generations to help predict its future occurrence.

What does a genetic counselor do when creating a pedigree?

They collect phenotypic data from family members and use it to construct the pedigree.

What does an 'О' symbol represent in a pedigree?

A male who is unaffected.

What does 'Ою' indicate in a pedigree?

Marriage between individuals.

What is represented by the symbol '□ O'?

An affected female.

What does the symbol 'до' signify in a pedigree?

A deceased individual.

What are the notable methods used in linkage analysis?

Linkage analysis identifies mutations using DNA markers and statistical analysis to track inheritance.

What types of DNA markers are used in linkage analysis?

Restriction Fragment Length Polymorphisms (RFLPs), Variable Number Tandem Repeats (VNTRs), and Short Tandem Repeats (STRs).

What is RFLP analysis?

A technique used to analyze DNA fragments by digesting them with restriction enzymes and separating them via gel electrophoresis.

Why is linkage analysis important for genetic disorders?

It helps determine carrier status and predict the presence of genetic disorders when mutations can't be directly identified.

What condition is characterized by a triad of pulmonary disease, pancreatic insufficiency, and salty sweat?

Cystic Fibrosis.

What gene mutation is responsible for Cystic Fibrosis?

Mutations in the CFTR gene.

What is the inheritance pattern of Cystic Fibrosis?

Autosomal recessive.

How is Duchenne Muscular Dystrophy inherited?

In an X-linked recessive pattern.

What protein is affected in Duchenne Muscular Dystrophy?

Dystrophin.

What is the most common mutation causing DMD?

Deletions spanning one or more exons.

What is the incidence of Duchenne Muscular Dystrophy in newborn males?

1 in 3,500 to 5,000.

What type of mutation is common in sickle cell disease?

A single base change causing a mutation in the hemoglobin beta chain.

How can sickle cell anemia be diagnosed?

Genetic screening through PCR to detect the specific mutation.

What defines Huntington's Disease?

A progressive brain disorder caused by a defective gene on chromosome 4.

What trinucleotide repeat is associated with Huntington's Disease?

CAG repeat.

How does the number of CAG repeats relate to Huntington's Disease?

More than 40 repeats indicate the condition.

What genetic condition results from a partial deletion on chromosome 4?

Wolf-Hirschhorn Syndrome.

What are the main phenotypic features of Wolf-Hirschhorn Syndrome?

Growth retardation, microcephaly, seizures, and congenital heart defects.

What is the average mortality rate for Wolf-Hirschhorn Syndrome within the first year?

35%.

What kind of testing can detect Wolf-Hirschhorn Syndrome?

High-resolution GTG banding, FISH, and chromosomal microarray.

What kind of analysis is used to examine RNA variants in Duchenne Muscular Dystrophy?

RNA analysis such as RT-PCR and RNA-seq.

What is the clinical utility of HLA typing in autoimmune disease?

To predict the relative risk of developing autoimmune conditions.

What type of inheritance does sickle cell anemia follow?

Autosomal recessive.

What kind of mutations account for 60–70% of DMD cases?

Deletions in the DMD gene.

How is the diagnosis of Cystic Fibrosis confirmed?

By genotyping the CFTR gene.*

What kind of mutations may lead to misfolded CFTR proteins?

Class III mutations.

What is an outcome of improper function of CFTR protein?

Disruption of fluid transport and mucus accumulation.

What symptoms characterize sickle cell disease?

Crescent-shaped red blood cells that can block blood flow, causing pain crises.

What measurement indicates a positive diagnosis for Huntington's Disease?

Greater than 40 CAG repeats identified through PCR.

What other disorders is HLA typing associated with?

Rheumatoid arthritis, diabetes mellitus, multiple sclerosis.

What are common therapies targeted at CFTR mutations?

Correctors and potentiators to improve CFTR function.

What is the link between CFTR mutations and sweat chloride levels?

Mutated CFTR leads to elevated sodium and chloride in sweat.

What is a significant feature of X-linked disorders in pedigrees?

Males are more frequently affected than females.

What is the frequency of Cystic Fibrosis in Caucasian newborns?

1 in 3,000.

What is a major challenge in diagnosing Duchenne Muscular Dystrophy?

Detecting mutations in such a large gene (DMD spans > 2,200 kb).

What may trigger the pathophysiology in Huntington's Disease?

Accumulation of the defective huntingtin protein.