Which of the following statements comparing the genetics of simple Mendelian disorders and schizophrenia is true?
B. The monozygotic concordance for simple Mendelian disorders is approximately 100%. This is because the penetrance is usually complete (though it may vary) in simple Mendelian disorders. In contrast, penetrance is incomplete in schizophrenia. Phenocopies of schizophrenia are very common; multiple organic and drug-induced states resemble schizophrenia. Locus heterogeneity in the same family is not a feature of simple Mendelian disorders affecting single loci. As the exact genetic localization of schizophrenia is still not certain, locus heterogeneity cannot be determined for schizophrenia, but given the multifactorial nature of schizophrenia, significant locus heterogeneity is very likely. Mendelian disorders need not necessarily present in childhood; many autosomal dominant disorders present clinically only in adulthood.
Reference:
The term copy number variation refers to:
A. The human genome is comprised of two sets of 23 chromosomes, one set inherited from each parent, and the DNA encodes 30 000 genes. Formerly, it was believed that genes were almost always present in two copies in a genome, but recently large segments of DNA of various sizes have been found to differ in copy number. Such copy-number variations (or CNVs) can lead to dosage imbalances in both functional (exons) and non-coding (introns) regions. As a result, many genes that were thought to occur in two copies per genome have now been found to be present in one, three, or even more copies.
From the following, chose the correct combination of trinucleotide repeats and fragile-X syndrome genotype:
D. Fragile-X patients have more than 200 CGG repeats in the 5’ untranslated region of the fragile-X mental retardation 1 gene (FXMR-1). As in other trinucleotide repeat diseases, these expansions originate from phenotypically normal individuals who carry an intermediate number of unstable repeats (60 to 200). Normal individuals have 6 to 60 repeats. Even in carriers with premutation, longer repeats are observed to be more toxic than shorter, near normal ones. These carriers may show evidence of a neurodegenerative condition distinct from fragile X. The degree of toxicity increases with abundance of the transcript. CAG repeats are seen in Huntington’s chorea.
Which of the following statements regarding genetic testing for Huntington’s disease is true?
A. Genetic testing for Huntington’s disease involves testing the person at risk for the presence of excessive DNA repeats that predict development of clinical features. The test cannot predict the age at which the onset of such symptoms could occur. Almost all patients carry a specific mutant gene at chromosome 4 and the inheritance has complete penetrance. Earlier genetic testing involved linkage analysis with only probabilistic estimates given to at-risk individuals. The tested individuals were given a risk estimate of less than 5% or greater than 95%, based on the results. Since 1993, direct identification of the trinucleotide expansion has been made possible, greatly increasing the accuracy of the test to nearly 100%. Being an autosomal dominant condition, the disease exhibits an all-or-none phenomenon; homozygotes are no more severely affected than heterozygotes. Prenatal testing is possible even when the at-risk parent has not had a test him/ herself. In this case, only the proportion of the parent’s risk that is passed on to the fetus can be estimated; often this may not give sufficient information to decide on termination of pregnancies. The disease can occur in persons with apparently no positive family history, though this is extremely rare nowadays.
A 12-year-old boy presents with clinical features consistent with hyperkinetic disorder with conduct problems. On examination, he has an abnormal spinal curvature. Psychometric testing reveals deficits in linguistic and visuospatial skills with borderline IQ. His younger brother has multiple, light-brown spots on his face.
Which of the following is the likely mode of inheritance?
A. This patient presents with neurofibromatosis type 1. Patients with neurofibromatosis can present with light-brown spots on the skin (café-au-lait spots), neurofibromas, freckling in the area of the armpit or the groin, hamartoma of the iris (Lisch nodules), optic glioma, and scoliosis. Many children with NF1 have larger than normal head circumference and may have congenital heart defects. They may have poor linguistic and visual–spatial skills, in addition to attention deficit hyperactivity disorder (ADHD). Most symptoms are notable before the age of 10. The genetic localization of NF1 points to chromosome 17. The NF1 gene codes for a protein called neurofibromin, which acts as a regulator of cell division in the CNS. A second type of neurofibromatosis is called NF2; the clinical presentation and genetic abnormality seen in NF2 are different from NF1. The gene responsible for NF2 has been identified on chromosome 22. The NF2 gene product codes a tumour-suppressor protein called merlin.