Anticipation (genetics)

About: Anticipation (genetics) is a research topic. Over the lifetime, 669 publications have been published within this topic receiving 21784 citations. The topic is also known as: Genetic Anticipation & Anticipation, Genetic.

V2 receptor antagonists in cystic kidney diseases: an exciting step towards a practical treatment.

Abstract: It is unusual in nephrology for the fruits of basic science research in genetics and cell biology to directly translate into a practical therapy for common renal diseases. Therefore it is with great anticipation that the clinical and research communities receive publications like the article by Wang

Genetic anticipation in BRCA1/BRCA2 families after controlling for ascertainment bias and cohort effect.

Abstract: Background Genetic anticipation, the earlier onset of disease in successive generations, has been reported in hereditary breast and ovarian cancer syndrome (HBOC), but little is known about its underlying mechanisms. Ascertainment bias has been suggested as a reason in previous studies. Likewise, cohort effect, which may be caused by environmental factors, can be misinterpreted as genetic anticipation. Methods The authors reviewed the pedigrees of 176 kindreds, segregating those with deleterious mutations in breast cancer genes 1 and 2 (BRCA1/BRCA2) who had at least 2 consecutive generations of the same cancer (breast or ovarian). By using mutation probabilities as analytical weights in weighted random-effect models, generational differences in the age at onset of breast/ovarian cancer were calculated. The analyses were further controlled for ascertainment bias by excluding probands and adjusting for birth-cohort effect in the anticipation models. Results The mean age at the onset of breast cancer for the probands' generation was 41.9 years, which was 6.8 years and 9.8 years earlier than the parents' and grandparents' generations, respectively. The anticipation effect for breast cancer remained significant after excluding the probands. There was a birth-cohort effect: patients who were born in 1930s and 1940s had breast cancer 5.0 years and 7.6 years earlier than patients who were born before 1920. The difference in breast cancer age of onset across generations was no longer significant after adjusting for birth-cohort effect. Conclusions The observed anticipation effect was driven mainly by a decrease in age of onset across birth cohorts, underscoring the need for risk-reducing interventions that target changing environmental/lifestyle factors in BRCA1/BRCA2 carriers. Cancer 2016;122:1913-20. © 2016 American Cancer Society.

Anticipation in schizophrenia: No evidence of expanded CAG/CTG repeat sequences in French families and sporadic cases

Abstract: A decrease in age of onset of schizophrenia through consecutive family generations (anticipation) has been found in several studies. Anticipation is known to result from expansion of CAG repeats in genes that determine several neurodegenerative disorders. In a previous study we analysed 26 unilineal two-generation French pedigrees and found clinical evidence of anticipation. A 10-year mean reduction in age of onset of schizophrenia was found in the second generation compared with the parental generation. The repeat expansion detection method was used to screen for CAG expansion in 21 of the 26 families with evidence of anticipation for the disease and in 59 sporadic schizophrenics and 59 controls. Comparison of the frequency distributions of CAG/CTG repeat size observed in schizophrenics and controls showed no significant difference, even when we considered familial (P = 0.23) and sporadic (P = 0.25) affected individuals separately. These results do not support the association between long CAG repeats and schizophrenia. However, the possibility that expansions with fewer than 40 repeats are involved in schizophrenia cannot be excluded.

Anticipation is not associated with CAG repeat expansion in parent-offspring pairs of patients affected with schizophrenia.

Abstract: With the rationale that a disease that presents with anticipation could be associated with expansion of trinucleotide repeats, we selected parent-offspring pairs of schizophrenia patients with earlier age at onset in the filial generation to measure the expansion of CAG repeats using the repeat expansion detection (RED) method. Intergenerational comparisons were made for age at onset, length of CAG repeats, and clinical variables. Although the patients from the filial generation became affected 13 years earlier than the parents (P < 0.0005), we did not find larger CAG repeats in the offspring. No association was found between size of CAG repeat and age at onset or with any other clinical variable. Overall, the frequency of patients with CAG repeats longer than 40 was 32%, which was similar to that observed in control subjects (27%). It is particularly noteworthy that in 86% of the pairs, the mother was the affected parent. In this Spanish sample with parent-offspring pairs presenting schizophrenia with clinical anticipation and apparent female bias of transmission, neither the phenomenon of anticipation nor disease status was associated with the expansion of CAG repeats.