Human Genetics III: Mendelian exceptions and Genomic Imprinting

Flashcards covering Mendelian exceptions, non-Mendelian inheritance, dynamic mutations, anticipation, epigenetics, genomic imprinting, and specific disorders like Huntington Disease, Myotonic Dystrophy, Fragile X syndrome, Beckwith-Wiedemann, Prader-Willi, and Angelman Syndromes.

What is codominance in genetics?

A mode of inheritance where both alleles of a gene contribute to the phenotype of the heterozygote, expressing both traits fully.

What is pseudoautosomal inheritance?

Inheritance involving homologous loci on the X and Y chromosomes (pseudoautosomal regions) that behave like autosomal genes and can show male-to-male inheritance.

What are dynamic mutations?

Mutations caused by repeat expansions, most commonly trinucleotide repeats, where wild-type alleles are polymorphic.

What genetic phenomenon is associated with dynamic mutations, characterized by earlier disease onset with successive generations?

Anticipation.

Identify the key features of Huntington Disease as a dynamic mutation disorder.

Autosomal dominant inheritance, CAG trinucleotide repeat in the 5' translated region of chromosome 4p16.3, affecting Huntingtin protein, and causing chorea, cognitive impairment, dementia, and mood changes.

Identify the key features of Myotonic Dystrophy as a dynamic mutation disorder.

Autosomal dominant inheritance, CTG trinucleotide repeat in the 3' untranslated region of chromosome 19q13.3, affecting MD protein kinase (DMPK), and causing progressive muscle weakness, myotonia, cataracts, and cardiac conduction defects.

What is Fragile X syndrome?

The most common form of inherited moderate intellectual disability, caused by a CGG expansion (>200 repeats) in the FMR1 gene, leading to excessive methylation of its promoter and reduced penetrance in females.

What are some characteristic physical features of Fragile X syndrome?

Long face with long palpebral fissures, broad philtrum, prominent forehead, protruding ears, high-arched palate, hyperextensible finger joints, and postpubertal macroorchidism.

What is epigenetics?

Influences on gene regulation that occur without altering the underlying DNA sequence, such as histone modification, non-coding RNA, and DNA methylation.

What is genomic imprinting?

An epigenetic phenomenon where genes are expressed in a parent-of-origin specific manner, involving the addition of chemical tags (e.g., DNA methylation) to CpG islands during gamete formation, affecting gene expression but not the DNA sequence.

Provide examples of genes influenced by genomic imprinting.

IGF2, which is only expressed from the paternal allele, and H19, which is expressed from the maternal allele.

What causes Beckwith-Wiedemann syndrome?

It is associated with chromosome 11p15.5 and involves overactivity of IGF2 and loss of function of CDKN1C, often due to 20-30% uniparental paternal disomy or 50-60% improper maternal methylation.

What are the clinical features of Beckwith-Wiedemann syndrome?

Overgrowth (macrosomia, hemihyperplasia), macroglossia, abdominal wall defects (omphalocele, umbilical hernia), hypoglycemia in newborns, increased cancer risk (Wilms tumor, hepatoblastoma), and ear anomalies.

How are Prader-Willi syndrome (PWS) and Angelman syndrome (AS) genetically related?

Both are often caused by a small deletion in the 15q11.2-q13 region, where a deletion on the paternal chromosome 15 results in PWS, and a deletion on the maternal chromosome 15 results in AS.

What is another genetic mechanism that can cause Angelman syndrome?

A mutation in the UBE3A gene.