genetics sg questions

Outline the range of molecular and cellular technologies being developed to enable therapies for human genetic diseases in the context of regenerative medicine

These technologies include CRISPR gene editing, stem cell therapy, gene therapy techniques, and tissue engineering approaches that aim to repair or replace damaged tissues and correct genetic defects.

CRSPR

Explain why genetically complex disorders are challenging to study and treat (30 marks) outline how genetic association studies and gene expression profiling may identify susceptibility genes and therapeutic targets

Genetically complex disorders involve multiple genes and environmental factors, making it difficult to pinpoint specific causes and develop effective treatments. Genetic association studies and gene expression profiling can reveal susceptibility genes and potential therapeutic targets by analyzing patterns and variations in a population.

Describe how chromosomal abnormalities cause disease. Illustrate using a diagram, why some children of healthy individuals with balanced reciprocal translocations may be affected by severe disease

Chromosomal abnormalities, such as deletions, duplications, and translocations, can disrupt normal gene function and lead to various diseases, including cancer and genetic disorders. In balanced reciprocal translocations, healthy parents may carry rearranged chromosomes that can segregate abnormally during meiosis, resulting in gametes with unbalanced genetic material, potentially causing severe diseases in offspring.

Discuss how the x chromosome continues to sex difference in disease susceptibility, and variable severity in females

The X chromosome carries many genes that influence susceptibility to various diseases, which can manifest differently in males and females due to X-linked inheritance patterns. Females, having two X chromosomes, may experience variable severity of diseases due to one X being potentially compensatory for the other, leading to differences in phenotype expression.

Discuss how dna triplet repeat expansions cause disease using examples of repeat expansions in both coding and non-coding DNA

DNA triplet repeat expansions result in the repetition of specific nucleotide sequences, leading to various diseases such as Huntington's disease and myotonic dystrophy. In coding regions, these expansions can disrupt protein function, while in non-coding regions, they may affect gene regulation and expression.

Describe the main types of cancer genes that have been identified and outline their involvement in the regulation of cell division

Cancer genes can be classified into three main types: oncogenes, tumor suppressor genes, and DNA repair genes. Oncogenes promote cell division and survival, tumor suppressor genes inhibit cell division, and DNA repair genes maintain genomic integrity; mutations in these genes can lead to uncontrolled cell growth and cancer.

Describe the diseases caused by mutations in the androgen receptor gene

Mutations in the androgen receptor gene can lead to a range of disorders, primarily androgen insensitivity syndrome, which causes individuals with XY chromosomes to develop female or ambiguous external genitalia despite having male internal reproductive structures. This disruption in the receptor impairs the body's ability to respond to androgens, leading to various degrees of male-to-female phenotypic variation.

Describe the causes and symptoms of down syndrome. Outline how maternal age affects its incidence

Down syndrome, caused by an extra copy of chromosome 21 (trisomy 21), leads to developmental delays and characteristic physical features. Increased maternal age, particularly women over 35, significantly raises the risk of chromosomal abnormalities during meiosis, contributing to a higher incidence of Down syndrome.

Describe the diseases caused by mutations at the androgen receptor locus (70 marks). Explain how the androgen receptor CAG repeat is used to estimate skewing of X chromosome inactivation in females (30 marks). Use diagrams where appropriate

This question addresses the impact of mutations at the androgen receptor locus, including androgen insensitivity syndrome and other related conditions. It also requires an explanation of how analyzing the CAG repeat length in the androgen receptor gene can help determine the skewing of X chromosome inactivation in females, potentially affecting phenotypic outcomes.

Discuss how DNA variation underpinning human diseases can be identified using genetic linkage and association studies (80 marks). Explain the term ‘linkage disequilibrium’ (20 marks). Use diagrams where appropriate

Genetic linkage and association studies uncover DNA variations related to human diseases by examining the inheritance patterns of alleles in families and the frequency of specific genetic variants in affected populations. Linkage disequilibrium refers to the non-random association of alleles at different loci, which can provide insights into genetic associations with diseases.

Describe the current methods that are used to modify the genome of the mouse to create models of human disease

Current methods for genome modification in mice include CRISPR/Cas9 gene editing, homologous recombination, and transgenic approaches. These techniques allow researchers to introduce specific mutations or genetic alterations that mimic human diseases, facilitating the study of genetic functions and potential therapeutic interventions.

Describe the different types of chromosomal abnormalities that cause human disease. Ecplain using a diagram why the children of an individual carrying a balanced reciprocal translocation may be affected by severe disease

Chromosomal abnormalities include numerical anomalies like aneuploidy (e.g., Down syndrome) and structural changes such as deletions, duplications, inversions, and translocations. Children of an individual with a balanced reciprocal translocation may inherit unbalanced chromosome arrangements, leading to gene dosage imbalances that can result in severe developmental and health issues.

in a short essay outline the contribution of triplet repeat expansions to human disease and describe the techniques you could use to confirm the presence of a repeat expansion.

Triplet repeat expansions refer to the abnormal replication of sequences of three nucleotide bases in DNA, leading to various genetic disorders such as Huntington's disease and fragile X syndrome. Techniques to confirm the presence of a repeat expansion include polymerase chain reaction (PCR), Southern blotting, and next-generation sequencing, which can detect and quantify the number of repeats present.

in a short essay Write an account of the approaches being developed to treat human diseases using genetic and cellular therapies.

Genetic and cellular therapies involve innovative strategies such as gene editing (e.g., CRISPR/Cas9), gene replacement, RNA interference, and stem cell therapies. These approaches aim to correct genetic defects, restore normal cellular function, and provide potential cures for hereditary and acquired diseases.

what are the modes of inheritance

Modes of inheritance refer to the patterns by which traits and genetic disorders are passed from parents to offspring. Common modes include autosomal dominant, autosomal recessive, X-linked dominant, and X-linked recessive inheritance.

define autosomal dominant and explain what a pedigree with it would look like

Autosomal dominant refers to a mode of inheritance where a single copy of a mutated gene from one parent can cause the expression of a specific trait or disorder. In a pedigree, this pattern is typically characterized by affected individuals appearing in every generation, with both males and females equally affected.

define autosomal recessive and explain what a pedigree with it would look like

Autosomal recessive refers to a mode of inheritance where two copies of a mutated gene, one from each parent, are required to express a specific trait or disorder. In a pedigree, this pattern often shows affected individuals who may not appear in every generation, with carriers (unaffected individuals with one copy of the mutated gene) often propagating the trait.

define X-linked recessive inheritance and explain what a pedigree with it would look like

X-linked recessive inheritance is a mode where a mutation on the X chromosome causes the expression of a trait or disorder primarily in males, as they have only one X chromosome. In a pedigree, affected males typically do not pass the trait to their sons but can pass it to daughters, who become carriers; affected daughters will have affected fathers.

define X-linked dominant inheritance and explain what a pedigree with it would look like

X-linked dominant inheritance is a mode where a mutation on the X chromosome can cause the expression of a trait or disorder in both males and females, although it is usually more severe in males. In a pedigree, affected males pass the trait to all their daughters but none of their sons, while affected females have a 50% chance of passing the trait to both sons and daughters.

define mitochondrial inheritance and explain what a pedigree showing it would look like

Mitochondrial inheritance refers to the transmission of genetic material found in mitochondria, which is passed exclusively from mother to offspring. In a pedigree, all children of an affected mother may show the trait, whereas children of an affected father will not, reflecting the maternal lineage of inheritance.

Describe key phenotypic features of Down syndrome and how to identify it on a chromosomal smear

Down syndrome is characterized by distinct phenotypic features including hypotonia, facial dysmorphism (such as a flat facial profile and slanted eyes), and a single transverse palmar crease. On a chromosomal smear, it can be identified by the presence of an extra copy of chromosome 21, resulting in a total of 47 chromosomes instead of the typical 46.

chromosomes for a female vs a male

Typically, females have two X chromosomes (XX), while males have one X and one Y chromosome (XY), determining their sex characteristics.

what factor is known as the gaurdian of the genome

The factor known as the guardian of the genome is p53, a tumor suppressor protein that regulates the cell cycle and prevents genomic mutations.

is p53 a tumour suppressor or a proto-oncogene

p53 is a tumor suppressor protein that helps prevent cancer formation by regulating the cell cycle and promoting apoptosis in damaged cells.

Provide a brief written account of how this p53 causes diseas

Inactivation or mutations in p53 can lead to uncontrolled cell proliferation and prevent the normal process of apoptosis, contributing to tumorigenesis and cancer progression.

Outline the various approaches and techniques you could use to identify the genetic components underlying a human disease.

These approaches include genome-wide association studies (GWAS), whole exome sequencing, linkage analysis, and candidate gene studies that investigate specific genetic variations associated with the disease.

Briefly describe the methods used to produce animal models of human genetic diseases.

Methods include the use of gene editing techniques like CRISPR-Cas9, transgenic approaches to introduce human genes into animals, and the use of knockout models to disrupt specific genes in order to study the effects on disease development.

Describe the genetic and epigenetic mechanisms that explain the a cat with a multi-colored coats phenotype. You may use an original diagram to illustrate your answer.

The multi-colored coat phenotype in cats is influenced by genetic factors such as the presence of the X chromosome that carries the orange (O) gene and epigenetic mechanisms that regulate gene expression. The random X-inactivation leads to a mosaic pattern of fur colors, resulting in the distinct coat appearance.

What is LOI?

LOI, or Loss of Imprinting, refers to the disruption of normal genomic imprinting, which can lead to abnormal gene expression and is associated with various genetic disorders.

What disease is caused by LOI at this IGF2 H19?

Come back

Describe how genetic linkage and genetic association studies are used to identify genetic variants that contribute to human disease (90 marks). Briefly outline what is meant by a ‘tagging SNP’ (10 marks).

Genetic linkage studies track the inheritance of disease-related traits in families to identify genes associated with diseases, while genetic association studies examine the correlation between specific genetic variants, like SNPs, and diseases within populations. A ‘tagging SNP’ is a single nucleotide polymorphism that is associated with a larger set of variants, enabling researchers to capture the genetic information of nearby alleles.

Discuss the multistep nature of carcinogenesis. In your answer, outline the major classes of genes associated with malignant transformation that would have been identified and their associated cellular pathways.

Carcinogenesis is a multistep process involving the accumulation of genetic and epigenetic changes that lead to cancer. Key gene classes associated with malignant transformation include oncogenes, tumor suppressor genes, and DNA repair genes, which affect pathways such as cell cycle regulation, apoptosis, and genomic integrity.

Describe the current methods that are used to modify the genome of the mouse to create models of human disease.

Current methods for modifying the mouse genome to create models of human disease include CRISPR/Cas9 gene editing, transgenic approaches that introduce foreign genes, and knockout techniques that disrupt specific genes, allowing researchers to study the role of these alterations in disease progression and mechanism.

Describe the different types of chromosomal abnormalities that cause human disease (80 marks). Explain, using a diagram, why the children of an individual carrying a balanced reciprocal translocation may be affected by severe disease (20 marks).

Chromosomal abnormalities refer to structural or numerical changes in chromosomes that can lead to various human diseases. These include deletions, duplications, inversions, translocations, and aneuploidies, which can disrupt gene function and regulation, leading to conditions such as Down syndrome, Turner syndrome, and other genetic disorders.

Discuss the evidence that tumour formation is a multistep process. In your answer, describe the main classes of genes that are mutates in cancer

Tumor formation is supported by evidence of sequential genetic alterations that lead to malignant transformation, demonstrating that multiple genetic changes occur over time. The main classes of mutated genes in cancer include oncogenes, which promote cell division; tumor suppressor genes, which normally inhibit growth; and DNA repair genes, which maintain genomic stability.

Describe the opportunities and challenges associated with the use of human gene therapy

Human gene therapy involves the introduction, removal, or alteration of genetic material within a patient's cells to treat diseases. Opportunities include potential cures for genetic disorders and improved treatments for cancer, while challenges include delivery mechanisms, immune responses, and ethical considerations.

Explain the molecular mechanism that causes “anticipation” in the context of human genetic disease. Descibe the clinical features of one such disease in detail

Anticipation refers to the phenomenon where genetic disorders appear at an earlier age or with increased severity in successive generations, often due to unstable repeat expansions in specific genes. One well-known disease exhibiting anticipation is Huntington's disease, characterized by progressive motor dysfunction, cognitive decline, and psychiatric symptoms.

Describe the casue and clinical features of downs syndrome, and explain how maternal age affects its incidence

Down syndrome is caused by the presence of an extra copy of chromosome 21, resulting in a total of three copies (trisomy 21). Clinical features include developmental delays, characteristic facial features, and an increased risk of congenital heart defects. Maternal age is a significant risk factor, as the likelihood of having a child with Down syndrome increases with older maternal age.

Describe how genetic linkage and genetic association studies are used to identify variants that contribute to human disease

Genetic linkage studies track inheritance patterns in families to find chromosomal regions associated with diseases, while genetic association studies analyze the frequency of variants in populations to identify associations with specific traits or conditions. Both methods contribute to understanding the genetic basis of human diseases.

Describe the types of diseases casued by mutation of the locus encoding the androgen receptor

Diseases such as androgen insensitivity syndrome and Kennedy's disease are caused by mutations in the androgen receptor locus, leading to disrupted male sexual development and motor neuron degeneration, respectively.

Describe the different types of chromosomal abnormalities that cause human disease. In your answer, use a diagra, to show why the children of healthy individuals with blaances reciprocal translocations may be affected by severe disease

Chromosomal abnormalities can include deletions, duplications, inversions, and translocations. These abnormalities can lead to diseases such as Down syndrome, Turner syndrome, and others. Balanced reciprocal translocations can result in unbalanced gametes, leading to offspring with genetic disorders.

Describe the main methods used to modify the genome of the mouse to create models of human disease

Techniques such as CRISPR/Cas9, homologous recombination, and transgenic approaches are employed to modify the mouse genome. These methods allow researchers to introduce specific mutations, delete genes, or insert foreign DNA to study disease mechanisms and potential therapies.

CRSPR (clustered regulatory interspaced short palindromic repeats)

is a revolutionary gene-editing technology that allows for precise modifications of DNA sequences. It uses a guide RNA to direct the Cas9 nuclease to specific genomic sites, enabling researchers to cut, insert, or delete genes in various organisms.

• efficient and highly targeted way to create doble strand break

• genome engineering

  • base editing

  • epigenic modifications