Patterns of Inheritance: Mendelian and Non-Mendelian
Merlin G. Butler, F. John Meaney in Genetics of Developmental Disabilities, 2019
Genetic heterogeneity refers to the development of the same or a similar phenotype by different genetic mechanisms and specifically addresses autosomal recessive conditions. For example, the genetics of hearing loss can represent genetic heterogeneity whereby dozens of recessive genes can lead to hearing loss. Additionally, through assortative or nonrandom mating a mate is selected with preference for a particular trait e.g., hearing loss, and genetic heterogeneity may exist. If both parents have the same autosomal recessive gene causing hearing loss, then all of their children would be anticipated to be affected with hearing loss (i.e., each parent would donate a recessive allele). Often hearing loss is not present in children born to parents with hearing loss even though the parents have an autosomal recessive form of hearing loss. This scenario can best be explained by both parents not having the same recessive gene for hearing loss. Thus, their children are unaffected but are carriers (heterozygous) for two different recessive genes causing hearing loss.
Clinical cancer genetics
Pat Price, Karol Sikora in Treatment of Cancer, 2014
Familial clustering of the same type of cancer may be due to more than one type of cancer pre-disposition gene. This is termed genetic heterogeneity. For example, familial breast cancer, in which there are clusters of >four cases of breast cancer at <60 years of age in the same lineage, may be due to mutations in either the BRCA1 or BRCA2 gene (breast cancer genes 1 and 2). However, calculations from the Breast Cancer Linkage Consortium,2 which collates international data from breast cancer families, have suggested that 63% of such families cases are due to mutations in either BRCA1 or BRCA2. Cases in the remaining 37% of families are rarely due to mutations in genes in the DNA repair pathway and the majority of the rest are likely to be due to gene(s) that remain to be discovered.
Pre-Sacral Tumours
Peter Sagar, Andrew G. Hill, Charles H. Knowles, Stefan Post, Willem A. Bemelman, Patricia L. Roberts, Susan Galandiuk, John R.T. Monson, Michael R.B. Keighley, Norman S. Williams in Keighley & Williams’ Surgery of the Anus, Rectum and Colon, 2019
Some patients who present with a presacral tumour will have a rare genetic syndrome: the Currarino syndrome. This is characterised by an autosomal dominant inheritance pattern with a classic triad of findings: 1) sacral anomalies, particularly a ‘sickle-shaped’ sacrum (‘scimitar sign’ on imaging); 2) presacral masses – usually anterior sacral meningocele or teratoma and 3) anorectal malformations. The demonstrated phenotype may vary, and there is a spectrum of disease. The mutation associated with this syndrome has been isolated to the HLXB9 gene on chromosome 7q36.25 There may exist some genetic heterogeneity, as the same mutation is not always seen, particularly in sporadic cases.26 The main clinical finding that should initiate a detailed family history and gene testing is the finding of the specific sacral anomaly, which is distinct for this syndrome.
Inherited retinal degeneration current genetics practices – a needs assessment
Published in Ophthalmic Genetics, 2020
Sydney Strait, Rebecca Loman, Lindsay Erickson, Meghan DeBenedictis
Inherited retinal degenerations (IRDs) affect approximately 1 in 3500 individuals in Europe and North America (1). IRDs are phenotypically and genetically heterogenous conditions that result in vision loss due to gradual loss of photoreceptor cell function (2). Genetic heterogeneity refers to a single phenotype caused by multiple different single genes. This can make genetic testing and clinical diagnosis for IRDs difficult for clinicians, patients, and families. However, proper diagnosis of patients with an IRD is important to understand the natural history and inheritance of the condition, and to provide information about clinical trials and possible treatment options. Furthermore, it is important to have a precise molecular diagnosis as some IRDs are due to a syndromic condition where the patient may have systemic health risks. To establish a clinical diagnosis, the American Academy of Ophthalmology (AAO) recommends clinical assessment of patients with IRDs to include thorough documentation of medical, ocular, and family history (2). Advances in genetic testing have allowed for a molecular diagnosis to be identified in over 50% of patients (3). Due to the heterogenous nature of this group of diseases with over 330 disease-causing genes identified to date, the AAO discusses the role of genetic testing as an appropriate measure to help aid in the diagnosis, prognosis, and management for this patient population (2,4,5). This begs the question: What genetics related practices are ophthalmologists and optometrists currently utilizing for patients with IRDs, and what resources could enhance current practices?
Ocular Manifestations of Neuronal Ceroid Lipofuscinoses
Published in Seminars in Ophthalmology, 2021
Rohan Bir Singh, Prakash Gupta, Akash Kartik, Naba Farooqui, Sachi Singhal, Sukhman Shergill, Kanwar Partap Singh, Aniruddha Agarwal
Massive neuronal loss and accumulation of intracellular acidic sphingomyelinase are the predominant features in all patients. Moreover, genetic heterogeneity adds to this challenge. Urine sediment dolichol levels are elevated in both types – it’s a nonspecific but helpful finding. Neuroradiological findings in CLN-4 disease: include parieto-occipital cortical atrophy, cerebellar atrophy, hyperintense periventricular areas; and periventricular thinning and enlargement.98–100A cortical layer-specific loss of neurons has been described in layers 2 and 3 for CLN-4 disease, and EEG in the patients reveals a slow background, polyphasic spikes, and slow-wave changes.7,100,101 These changes can most reliably be confirmed by invasive brain biopsy.96 The diagnosis remains neuropathological, and despite the rarity of disease and absence of noninvasive diagnostic techniques, several criteria and guidelines are being developed by experts.89
Replication of a genome-wide association study on essential hypertension in Mongolians
Published in Clinical and Experimental Hypertension, 2018
Hongmei Li, Tong Wu, Shaoqing Wang, Xueyan Li, Yongqiang Qiu, Chunrong Lin, Changchun Qiu, Zhihui Deng, Li Zhou, Xiaojie Zhang
Genetic heterogeneity is an inevitable problem in finding causative genetic effects of EH as well as other polygenic diseases but this can be avoided to some extent by analyzing homogeneous populations. In fact, Mongolian population of China, both farmers and herdsmen, have lived in Inner Mongolian Autonomous Region over thousands of years. Individuals recruited in this study were relatively homogeneous with regard to ethnicity, socioeconomic status, and occupational and dietary exposure. Thus, a study with genetic homogeneous population may increase statistical power for identification of relevant gene (33). Although only a small fraction of the top polymorphisms with genomic significance have been successfully replicated in this study, our findings are still very convictive because Tibetans share substantial genetic components with Mongolians based on the fact that more than 500 years ago, the nomadic Mongolians migrated from the Mongol steppes to the northeastern section of the Qinghai-Tibetan Plateau (34–36). Tibetans and Mongolians share ancestor within 25 generations since Mongolians’ arrival into Qinghai-Tibetan Plateau (37).
Related Knowledge Centers
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