Mendel Law of Inheritance Huntington Disease Discussion

Mendel and Human Genetics

COLLAPSE

Mendel did most of his work using pea plants and was studding seven different characteristics, each with two contrasting traits [1]. Morgan rediscovered his laws of inheritance and further the knowledge using Drosophila as a model organism. Later discoveries confirmed that human heredity is regulated by the same laws of inheritance. Many of our characteristics are polygenic, however a number of them are controlled by a single gene, and Mendel’s work is a “solid foundation for our current understanding of single-gene diseases in humans” [2]. 

Please search in the literature and present human disorder(s) that are following Mendelian type of inheritance.

1. https://opentextbc.ca/conceptsofbiology1stcanadianedition/chapter/8-1-mendels-experiments/

2. Chial, H. (2008) Mendelian genetics: Patterns of inheritance and single-gene disorders. Nature Education 1(1):63.

Here’s 1 Nerogica Nimalan

RE: Mendel and Human Genetics

COLLAPSE

The understanding of single-gene diseases humans helps to expand our knowledge on disorders that affect humans. Monogenic disorders are diseases that are caused by a variation in one single gene. An example of a single-gene disease is phenylketonuria. This disease is autosomal recessive and caused by an inborn error of metabolism. This means that there is a deficiency of phenylalanine hydroxylase which is an enzyme that causes the catalyzation of hydroxylation of phenylalanine to tyrosine. This disorder causes mental retardation. Another single-gene disorder is Huntington’s disease. This disease is an autosomal dominant disorder. This disorder is caused by a trinucleotide CAG repeat expansion in the specific huntingtin gene.

Citations:

Myers RH. Huntington’s disease genetics. NeuroRx. 2004;1(2):255-262. doi:10.1602/neurorx.1.2.255

Merritt AD, Conneally PM, Rahman NF, Drew AL. Juvenile Huntington’s chorea. In: Progress in neurogenetics. (Barbeau A, Brunette TR, eds), pp 645–650. Amsterdam: Excerpta Medica Foundation, 1969. 

Here’s 2. Ashley Lavdas

RE: Mendel and Human Genetics

COLLAPSE

Hello!

There are many diseases or syndromes that are caused by multiple genes influencing a trait, making it polygenic. However, there are a handful caused by only a single gene making it a monogenic inheritance pattern.

Fragile X syndrome is an X-linked dominant disorder that occurs by transcriptional silencing of the FMR1 gene (Garber et al., 2008). The FMR-1 gene has a repeating region of CGG in the 5’ untranslated region. Individuals with Fragile X syndrome have an expanded amount of repeats in this region that prevents synthesis of the gene’s protein product. The normal amount of CGG repeats on the FMR1 gene is between 6-55. “Pre-mutation” alleles have a higher number of repeats: 56-200. These pre-mutation alleles still provide a normal gene function, but they are unstable. During DNA replication in female germ-line cells, there is a high probability of CGG repeat expansion, thus pre-mutation alleles are unstable. Phenotypically normal females that are heterozygous for pre-mutation allele are likely to have gametes with a higher number of triplet repeats. When the CGG repeat is between 200-4000, it is considered mutant. When the FMR1 gene is mutated, the FMR1 protein can’t properly form synapses (Hartwell, 2018). FMRP, the gene product of FMR1, is a protein that negatively regulates the protein synthesis of neuronal dendrites. With a mutated gene, the transcripts that are normally regulated by FMRP are overtranslated and lead to an abundance of proteins that reduces synaptic strength (Garber et al., 2008).

Fragile X syndrome may not present phenotypically or only have subtle indications. However, it is associated with a wide range of intellectual and emotional disabilities, including autism (Garber et al., 2008).

References:

Garber, K. B., Visootsak, J., & Warren, S. T. (2008). Fragile X syndrome. European Journal of Human Genetics, 16(6), 666–672. doi:10.1038/ejhg.2008.61

Hartwell, L. (2018). Genetics: From genes to genomes (Sixth edition). McGraw-Hill Education.