5.2 Flashcards
(12 cards)
- What is the scope and impact of genetic disorders on the human population across a lifespan?
Genetic disorders are highly prevalent, with a lifetime frequency of about 670 per 1000 individuals, affecting approximately 8% of the population. Moreover, up to 50% of early miscarriages are associated with chromosomal abnormalities, and around 1% of all newborns exhibit a gross chromosomal abnormality, highlighting their significant impact from prenatal life onward.
- What are the three main categories of human genetic disease, and can you provide examples for each?
The three main categories are: (1) Chromosomal Disorders – for example, Down syndrome (trisomy 21) and Turner syndrome; (2) Single-Gene Disorders – such as sickle cell anaemia, cystic fibrosis, and Marfan syndrome; (3) Polygenic/Multifactorial Disorders – where multiple genes interact with environmental factors, such as type 2 diabetes and ischemic heart disease.
- What defines a chromosomal disorder, and what is an example of a chromosomal structural abnormality?
Chromosomal disorders involve numerical or structural alterations of whole chromosomes. For instance, Down syndrome, caused by an extra copy of chromosome 21 (trisomy 21), and Cri du Chat syndrome, resulting from a deletion on the short arm of chromosome 5, are examples of chromosomal disorders.
- How are single-gene (monogenic) disorders inherited, and what are the three main patterns of inheritance?
Single-gene disorders are inherited in one of three patterns: autosomal dominant (only one mutated copy is needed, e.g., Marfan syndrome), autosomal recessive (two copies are required, e.g., cystic fibrosis or sickle cell anaemia), and X-linked (mutations on the X chromosome, often affecting males more severely, e.g., Duchenne muscular dystrophy or Fragile X syndrome).
- Can you explain autosomal dominant inheritance with an example?
In autosomal dominant inheritance, a single copy of a mutated gene is sufficient to cause the disease. An example is Marfan syndrome, where a mutation in the FBN1 gene leads to connective tissue abnormalities, affecting the heart, eyes, and skeleton. Each child of an affected parent has a 50% chance of inheriting the disorder.
- How does autosomal recessive inheritance work, and what is a representative example?
Autosomal recessive inheritance requires that both copies of a gene be mutated for the disease to manifest. Carriers, who have one normal and one mutated gene, are typically asymptomatic. Cystic fibrosis is a classic example, where two faulty CFTR genes lead to the disease.
- Describe X-linked inheritance and provide a typical example.
X-linked inheritance involves a mutation on the X chromosome. Since males have only one X chromosome, they are more affected by mutations. A common example is Duchenne muscular dystrophy, where mutations in the dystrophin gene lead to severe muscle degeneration, primarily in males, while females are usually carriers.
- What molecular mechanisms underlie genetic disorders, and what types of DNA alterations are involved?
Molecular mechanisms include point mutations (such as missense or nonsense mutations), insertions, deletions, copy number variations, and trinucleotide repeat expansions. These alterations can occur in coding or non-coding regions, leading to loss of function, gain of function, or toxic protein accumulation. For example, a point mutation in the CFTR gene causes cystic fibrosis, while trinucleotide repeat expansions in the FMR1 gene cause Fragile X syndrome.
- How do chromosomal structural alterations differ from single nucleotide mutations?
Chromosomal structural alterations involve large-scale changes such as translocations, inversions, duplications, or deletions affecting entire regions or multiple genes (e.g., the extra chromosome 21 in Down syndrome). In contrast, single nucleotide mutations affect only one base pair in the DNA and typically alter the function of a single gene, as seen in many monogenic disorders.
- What are polygenic or multifactorial disorders, and can you provide an example?
Polygenic or multifactorial disorders result from the combined effect of multiple genes (each with small individual effects) and environmental influences. Type 2 diabetes and ischemic heart disease are typical examples, where genetic predisposition interacts with lifestyle factors such as diet and exercise to determine disease risk.
- Why is understanding the molecular mechanisms of genetic diseases crucial for diagnosis and treatment?
Understanding molecular mechanisms helps pinpoint the exact genetic alteration responsible for a disorder, enabling precise diagnosis through genetic testing. This knowledge also guides the development of targeted therapies and informs genetic counselling and preventive strategies for at-risk individuals.
- How does the study of genetic inheritance and molecular pathology impact public health strategies?
By elucidating the inheritance patterns and underlying molecular mechanisms, healthcare providers can offer more accurate screening, early diagnosis, and personalized treatments. Moreover, public health initiatives can focus on modifiable risk factors in polygenic disorders and provide effective genetic counselling, ultimately reducing disease burden and improving health outcomes across the lifespan.
