A female is heterozygous for XR color blindness and is color-blind in one eye but not the other. Explain how this could occur.
Normally, one of the x-chromosomes would be 'inactivated' and form a Barr body. In this case, the patient may be mosaic - and one eye is exhibiting the recessive color-blind trait.
A major cause of spontaneous abortion is abnormalities of chromosome number. List the major categories and explain why they are usually lethal. What is the relative risk of recurrence?
Polypoidy: any multiple of the basic haploid chromosome number other than the diploid number; thus 3n, 4n, and so forth. Aneuploidy: any chromosome number that is not an exact multiple of the haploid number, so 2n+1 = trisomy, 2n-1 = monosomy. Most are lethal during development because of imbalance in gene products.
Describe the phenotype and genetic origin of 47XXY, including any maternal and paternal effects, if any. What is the risk of recurrence?
Klinefelter Syndrome occurs in 1/1000 male births, does not occur in females. This syndrome is proof that the Y chromosome is male determining. Phenotype: mental retardation, infertility, some secondary female characteristics. XXY, XXXY, XXXXY (extra Barr bodies). ~50% result from errors in paternal meiosis I. ~50% from errors in maternal meiosis I or meiosis II. Maternal age is increased in cases associated with maternal meiosis I errors. Very small risk of recurrence.
Describe the phenotype and genetic origin of Trisomy 21, including maternal and paternal effects, if any. What is the risk of recurrence?
Phenotype for Trisomy 21: males - sterile, females - fertile, growth failure, mental retardation, abnormal ears, broad flat face, slanting eyes, epicanthic eyefolds, big, wrinkled tongue; Three sets of genetic information for 21st chromosome (in 95% of cases), Robertsonian translocation of #14 or #22 (5% of cases). There is known to be a maternal age effect, no known pateral effects. Risk of recurrence is ~1%, and is higher in younger women. Also is higher if translocation is carried by parent.
What does epigenetics refer to and why is it important in medical genetics?
Epigenetics is an area of increasing importance in human and medical genetics, with significant influences on gene expression and phenotype both in normal individuals and in a variety of disorders including cytogenetic abnormalities, inherited single-gene conditions and cancer. The term refers to any factor that can affect gene function without change in the genotype. Some typical epigenetic factors involve alterations in DNA methylation, chromatin structure, histone modifications, and transcription factor binding that change genome structure and affect gene expression without changing the primary DNA sequence.
What is a chromosomal mosaic and how does it arise? What disorders might have instances due to mosaicism?
A mosaic is an individual with at least two cell lines differing in genotype or karyotype, derived from a single zygote. Can be caused by nondisjunction in an early postzygotic mitotic division. Conditions include Trisomy 21 and Klinefelter Syndrome.
What is a microarray (DNA chip) and why/how is it useful in human genetics?
A microarray is a miniaturized wafer ("chip") made of glass, plastic, or silicon onto which a large number of nucleic acids have been individually spotted. They may allow entire genomes or large collections of mRNA transcripts to be examined in a single experiment. It is usefule in screening for genetic disorders, gene copies and mutations.
What is chromosome banding? How is it useful in clinical genetics?
G-banding (giemsa stain) - basis for assigning gene locations, banding patterns helped figure out some disorders (ex- Trisomy 21)
What is FISH? How is it useful in clinical genetics?
Fluorescence in situ hybridization. The DNA, either in interphase chromatin or in metaphase chromosomes, is fixed on a slide and denatured in place (hence "in situ") to expose the two strands of DNA and allow a denatured labeled probe to hybridize to the chromosomal DNA. Can be used for karyotyping.
What is meant by personalized medicine? What kinds of diagnostic tests are used?
One of the major goals of the Human Genome Project - practice of medicine based on large-scale genomic information, such as expression profiling to characterize tumors or to define prognosis in cancer, genotyping of variants in genes involved in drug metabolism or action to determine an individual's correct therapeutic dosage, or analysis of multiple protein biomarkers to monitor therapy or to provide predictive information in presymptomatic individuals. Examples of diagnostic tests include FISH, Northern Blot, Microarrays, DNA chips, and DNA sequencing.
What is the approximate number of human genes? Explain in terms of molecular genetics why/how the proteome is much larger.
Current estimates are that the genome contains about 25,000 genes, but this figure only begins to hint at the levels of complexity that emerge from the decoding of this digital information. Many genes are capable of generating multiple different proteins, not just one. This can happen by alternate splicing, alternate promoters and RNA editing.